The Agency for Healthcare Research and Quality (AHRQ) recently identified the perioperative administration of beta-blockers as one of 11 specific practices with sufficient clinical-based evidence for patient safety to justify immediate and widespread implementation.1 A number of randomized, controlled trials support the use of beta-blockers to reduce the morbidity and mortality associated with non-cardiac surgery in patients at risk for cardiac events.2-5
Randomized clinical trials involving more than 24,000 patients demonstrated that beta adrenergic blockade reduced post-myocardial infarction mortality, likely by a reduction in infarct size when administered early or by a reduction in ventricular arrhythmias when administered chronically.6 In randomized clinical trials involving over 15,000 patients, beta-blockade also reduced the morbidity and mortality in patients suffering from congestive heart failure.7 All beta-blockers except those with intrinsic sympathetic activity reduce mortality in both myocardial infarction and heart failure patients.
Applying the above information from clinical trials to the perioperative care of the cardiovascular patient, it seems logical that beta-adrenergic blockers might be beneficial during the stressful surgical period. Four randomized controlled trials concerning the effectiveness of perioperative beta-blockade in reducing perioperative cardiac events are the basis for the AHRQ recommendations. In 1988, Stone et al.2 demonstrated that in 128 hypertensive patients having elective surgery, beta-blockade reduced the incidence of Holter monitored documented ischemia (2%) compared to a control group (28%) (p<0.001). Neither the types of surgery nor the baseline demographic data were reported in this study. Mangano et al.3 reported on patients undergoing elective noncardiac surgery who had received atenolol preoperatively and had this continued through the seventh postoperative day. The all-cause mortality at 2 years (p=0.019), cardiac death at 2 years (p=0.033), and postoperative ischemia (p=0.03) were significantly reduced in the atenolol treated patients compared to controls. Critics of this study point out less coronary disease, more ACE-inhibitors, and fewer incidents of discontinuing beta-blockers in the beta-blockade group. However, statistical analysis modeling for these differences upheld the overall conclusions of the study.
Two studies in 1999 continued the search for clinical data to validate the use of perioperative beta-blockade. Poldermans et al.4 randomized 112 patients with positive dobutamine stress echocardiograms having vascular surgery procedures to receive bisoprolol starting an average of 37 days before surgery and continuing for 30 days after surgery. Patients already taking beta-blockers were excluded. Cardiac death was 3.4% in the beta-blocker group and 17% in controls (p=0.02), and nonfatal MI was 0% in the beta-blocker group and 17% in controls (p<0.001). Raby et al.5 randomized 26 patients with Holter monitor documented preoperative ischemia undergoing vascular surgery to either a control group or to receive esmolol for 48 hours postoperatively, titrated to keep the heart rate at 20% below the individual ischemic threshold. Postoperative ischemia occurred in 33% of the beta-blocker group and in 73% of the controls (p<0.05). Other studies have been performed which tend to support perioperative beta-blockade but suffer from a lack of a true control group8 or inadequate sample size.9
Are there problems with administering beta-blockers perioperatively? Most would agree that in the patient already receiving beta-blockers, therapy should be continued postoperatively. The failure to maintain these drugs during this period may generate serious side effects secondary to withdrawal and an upregulated beta receptor state. Sinus bradycardia, heart failure, and bronchospasm are rare reported side effects in the clinical studies, but do occur. Esmolol, a short-acting beta-blocker, is therefore very attractive in patients who may have an increased risk for adverse effects but who would appear to benefit from therapy because of a high risk for cardiac complications. Furthermore, AHRQ recommends that beta-blockers be continued for 1 week postoperatively.
Does perioperative beta-blockade preclude preoperative screening and risk stratification? This remains a difficult question to answer. Certainly the use of beta-blockade perioperatively appears effective and could generate significant cost savings if preoperative testing is reduced. However, improved outcomes in high-risk patients may still result if critical coronary lesions (e.g., left main disease) are identified preoperatively. The various patient subgroups which might yield a positive cost-benefit analysis from aggressive preoperative testing remain to be identified.
The AHRQ stance on perioperative beta-blockade is clear. Additionally, further randomized, controlled clinical studies may be limited because of the reluctance of researchers to place patients in a placebo group due to patient safety concerns. Therefore, the perioperative use of beta-blocker therapy to prevent cardiac events and to reduce associated cardiac mortality may evolve to become a standard of care. Even though post-myocardial infarction beta-blockade is considered standard of care, it too remains disturbingly underutilized.10 A recent study in vascular surgery patients in Europe revealed that only 27% received perioperative beta-blockade.11 One can hope the AHRQ position will increase anesthesiologists’ and surgeons’ awareness of the benefits of perioperative beta-blockade in high-risk patients. Widespread implementation of this perioperative therapy will likely improve patient safety.
Dr. Royster is Professor and Vice Chair of the Department of Anesthesiology at 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.
- 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.
- Stevenson LW. Beta-blockers for stable heart failure. N Engl J Med 2002;346:1346-7.
- Chae CU, Hennekens CH. Beta blockers. In: Hennekens CH, ed. Clinical Trials in Cardiovascular Disease: A Companion to Braunwald’s Heart Disease. Philadelphia: W.B. Saunders, 1999:76-94.
- Harwood TN, Butterworth J, Prielipp RC, et al. The safety and effectiveness of esmolol in the perioperative period in patients undergoing abdominal aortic surgery. J Cardiothorac Vasc Anesth 1999;13:555-61.
- Urban MK, Markowitz SM, Gordon MA, et al. Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia. Anesth Analg 2000;90:1257-61.
- Krumholz HM, Radford MJ, Wang Y, et al. National use and effectiveness of beta-blockers for the treatment of elderly patients after acute myocardial infarction: National Cooperative Cardiovascular Project. JAMA 1998;280:623-9.
- Boersma E, Poldermans D, Bax JJ, et al. Predictors of cardiac events after major vascular surgery: role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. JAMA 2001;285:1865-73.