Although the Agency for Healthcare Research and Quality (AHRQ) has identified perioperative beta-blockade to have sufficient clinical-based evidence to justify widespread implementation,1 the application of this recommendation to clinical practice is less clear and guidelines need to be developed to help the busy clinician implement this into his practice. Which patients should receive beta-blockers? What drugs should be used? How long should beta-blockers be administered? These are some of the important questions that need to be addressed.
It is clear that the patients with the highest risk of perioperative cardiac events should receive perioperative beta-blockade. Patients with known coronary disease, positive preoperative stress examinations, patients with known risk factors for coronary disease having high-risk procedures (intraperitoneal and intrathoracic), and patients with diabetes mellitus requiring insulin therapy would likely benefit from perioperative beta-blockade.2 All of the randomized, controlled studies showing benefit from perioperative beta-blockade were in patients with probable or documented ischemic heart disease and most were in vascular surgery patients.3-6 It is unknown whether patients with valvular heart disease, or chronic heart failure, despite the proven benefit of beta-blockers in these disease states, would benefit from perioperative beta-blockade. Certainly, if the patient is treated with beta-blockers for mitral stenosis or heart failure, these medications should be continued to avoid the withdrawal syndrome of hypertension, tachycardia, and increased sympathetic activity in a situation in which beta receptor density is increased.
If the patient is not receiving beta-blockers, how should the physician implement beta-blocker therapy? The Poldermans study5 started beta-blockade 37 days before surgery and continued it for 30 days postoperatively. This is impractical in today’s busy operative environment unless the patients are started on beta-blockers by the surgeon or internist days in advance. However, even if the patient is seen the day before surgery, initiating oral beta-blockers that evening with another dose the morning of surgery, having intravenous beta-blockers available during surgery, and maintaining treatment as long as possible in the postoperative period (up to discharge) seems prudent and consistent with the literature. Indeed, three of the four randomized, controlled trials cited by the AHRQ started beta-blockers the morning of surgery and continued therapy from 2 to 7 days postoperatively.3,4,6 This obviously requires communication with the surgeon and other physicians caring for the patient in the postoperative period.
What is the endpoint for beta-blocker titration perioperatively? The most frequently used gauge of adequate beta-blockade has been heart rate control. However, it is not known whether heart rate control per se and the positive effects on myocardial oxygen supply and demand cause the reduced mortality or are just markers. Perhaps the true beneficial effect results from reduced perioperative arrhythmias, reduced likelihood of a plaque fracture, or reduced risk of thrombus formation from the anticoagulant effects of beta-blockers. Although most of the above studies achieved a heart less than 80 bpm, others have recommended a heart rate of 65 bpm or less.2
What beta-blockers should be used perioperatively? The cardioselective beta-blockers which include the long-acting atenolol, intermediate-acting metoprolol, and the short-acting esmolol are attractive from the perspective of the anesthesiologist because they are relatively familiar and can be given intravenously. If the patient is seen in the preoperative clinic, oral therapy can begin with atenolol 50 mg or bisoprolol 5-10 mg each day or metoprolol 25-50 mg twice a day, with instructions to the patient to watch for side effects and to call the clinic prior to surgery if side effects develop. If the patient is seen the day before surgery, atenolol 5-10 mg can be given intravenously or atenolol or metoprolol 5-10 mg titrated intravenously the morning of surgery. Certainly esmolol is an excellent drug for beta-blockade during surgery and postoperatively if the patient is in a unit where intravenous infusions are allowed. If not, then intravenous atenolol or metoprolol can be given until the patient can take oral atenolol or bisoprolol. The beta-blockers with intrinsic sympathomimetic activity should be avoided.
Anesthesiologists should be comfortable treating side effects from these drugs. Hypotension is due to decreased cardiac output and associated sinus bradycardia. Anticholinergics may or may not increase heart rate depending on the degree of beta-blockade. Increasing preload or even phenylephrine may help hypotension in patients with good ventricular function. If esmolol is being used intraoperatively, it can be decreased or discontinued with a quick offset due to a half-life of only 9 min. Ultimately, beta agonists such as ephedrine or beta-agonist infusions can provide competitive antagonism and effectively treat hypotension, but may counteract the advantages of preoperative beta-blockade. The side effects in the clinical studies were rare, only requiring anticholinergic treatment of sinus bradycardia.
It must be reemphasized that perioperative beta-blockade does not preclude preoperative testing in high-risk patients to rule out critical coronary lesions. However, it appears that physicians can reduce mortality in patients with a high prevalence of coronary disease having high-risk surgery by starting beta-blockers at least by the morning of surgery, using a target heart rate, and continuing beta-blockade for several days into the postoperative period.
Dr. Royster is Professor and Executive Vice Chair of the Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC.
- Shojania KG, Duncan BW, McDonald MD, et al. Making Health Care Safer: A Critical Analysis of Patient Safety Practices. Evidence Report/Technology Assessment No. 43 (Prepared by the University of California at San Francisco-Stanford Evidence-based Practice Center under Contract No. 290-97-0013), AHRQ Publication No. 01-E058, Rockville, MD: Agency for Healthcare Research and Quality. July 2001.
- Auerbach AD, Goldman L. Beta-blockers and reduction of cardiac events in noncardiac surgery. JAMA 2002;287:1435-1444.
- Stone JG, Foex P, Sear JW, et al. Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent. Anesthesiology 1988;68:495-500.
- Mangano DT, Layug EL, Wallace A, et al. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996;335:1713-20.
- Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999;341:1789-94.
- Raby KE, Brull SJ, Timimi F, et al. The effect of heart rate control on myocardial ischemia among high-risk patients after vascular surgery. Anesth Analg 1999;88:477-82.