Rationale: Tachycardia is the best correlate of intraoperative ischemia defined by ST depression during intraoperative monitoring. Prevention of this tachycardia has well documented clinical efficacy (Mangano et al, NEJM 335: 1713, 1996 and Poldermans et al, NEJM 341: 1789, 1999).

Candidates for therapy:

Mangano Criteria, 2 or more of the following risk factors

• Age > 65 years old
• Hypertension
• Current smoker
• Serum cholesterol > 240 mg/dl
• Diabetes Mellitus

• Age > 70 years old
• Prior MI by hx or Qs on ECG
• Compensated CHF or h/o CHF
• Current Rx for ventricular tachyarrythmias
• Current Rx for diabetes mellitus
• Limited Exercise Capacity (functional class III or IV)
• Dobutamine Echo positive if wall motion abnormality in one or more segments. Pt excluded if evidence of L main disease or 3 vessel disease.

• Congestive Heart Failure (rales MORE than 1/4 of the way up)
• 3rd degree heart block
• bronchospasm

Oral therapy:
Pts are started on atenolol 50 mg a day or equivalent (e.g. metoprolol 50 mg bid or bisoprolol 5 mg a day). At the next dose, if HR is > 65 and SBP is > 100, the pt has their dose increased to 100 mg atenolol (100 mg metoprolol bid or 10 mg bisoprolol). The medication is withheld if HR is < 55 or SBP < 100. Therapy is continued at least through hospitalization. The Poldermans study continued the medication for 30 days post-op, but Mangano treated the patient only while they remained in the hospital post-op.

IV therapy:
Atenolol, 5 mg given IV over 5 minutes, if HR > 65 and SBP > 100 5 minutes after completion of infusion, an additional 5 mg given IV. Exclusion criteria would also prevent additional IV dosing. 12 hrs after IV dosing, oral atenolol given. If HR >65 and SBP > 100, 100 mg given. If HR <65, but > 55, and SBP > 100 mm Hg, 50 mg given.
Pharmacodynamics affecting IV vs. oral dosing:

• Oral atenolol maximal effect 2-4 hrs.
• No first pass effect, but oral absorption about 50%.
• IV levels fall 5-10 fold over first 6hrs, then at rate similar to po doses.

1. Give 10 mg IV over 5 minutes
2. Repeat in 30 minutes, IF HR > 55 AND SBP >100 mm AND total dose administered IV is less than 40 mg.
3. Terminate when one of these endpoints is reached (i.e. HR < 55 OR SBP < 100 OR total IV dose 40 mg of metoprolol).
4. Define oral dose of metoprolol based on total IV dose administered. For each 10mg that was administered IV, the patient will receive 25 mg bid up to a maximal dose of 100 mg bid
5. Administer first oral dose 4 hours after last IV dose if < 50yo, 6 hours after last IV dose if > 50yo. As in Polderman, if HR <65, but > 55 and SBP > 100, give half the predicted dose.

• 50% first pass metabolism, bioavailability of PO dose increases with dose administered.
• Maximum beta blockade 20 minutes after IV infusion. Peak level after PO administration is 90 minutes
• Equivalent maximal beta-blocking effect achieved with PO vs. IV in 2.5 to 1 ratio.
• Half life is 4-8 hours, with the elderly more likely represented at the upper end.

PO protocol per Mangano and Poldermans’ papers.
IV atenolol protocol per Mangano paper.
IV metoprolol protocol extrapolation of atenolol protocol considering pharmacodynamics (as noted in PDR 1999 and AHFS Drug Information 2001) and Goteborg Protocol for IV metoprolol in acute MI (Lancet 2: 8251, 1981).