Esmolol for Treatment of Perioperative Tachycardia

• Efficacy of continuous perioperative infusion of esmolol [ Time Frame: 30 minutes prior to induction until 12 hours after surgery ] [ Designated as safety issue: Yes ]
  Duration of perioperative excursion (ie, time spent) outside Target HR range defined as 60 to 80 bpm during continuos infusion of esmolol from immediate pre-operative period up to 12 hours post-operatively, expressed as percent of time of esmolol infusion.
  
  

• Safety of continuous perioperative infusion of esmolol [ Time Frame: 30 minutes prior to induction until 12 hours after surgery ] [ Designated as safety issue: Yes ]
  Perioperative incidence of hypotension. In addition we will determine and assess incidence of ischemic adverse events (myocardial, cerebral, renal), the need for rescue therapy (therapy other than study drug) to maintain HR & BP target), the discontinuation rate of study drug, total infusion time to maintain a min SBP of 95 mmHg , total period of time patients are not in the target window of SBP > 95 mmHg, total period of time patients have bradycardia and a subgroup analysis to evaluate other non invasive hemodynamic parameters (e.g. CO, SV, SVV).
  
  

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.