March 1998

Prophylactic atenolol reduces postoperative myocardial ischemia.

Wallace A, Layug B, Tateo I, Li J, Hollenberg M, Browner W, Miller D, Mangano DT; Anesthesiology 1998; 88:1-7.

[ see abstract below ]

Beta-adrenergic blocking drugs - incredibly useful, incredibly under-utilized. (Editorial)
Warltier DC. Anesthesiology 1998; 88:2-4.
[ No Abstract Available ]

About 65 million Americans have cardiovascular disease, which causes about one million deaths per year. The implications for the morbidity and cost of medical care are impressive: about 25% of the 400,000 patients undergoing cardiac surgery per year and about 5% of the 30 million patients undergoing noncardiac surgery per year are likely to have some perioperative cardiovascular morbidity. It is estimated that these complications cost about $20 billion per year in medical treatment.

Well-known risk factors for the prediction of adverse perioperative cardiac outcome include congestive heart failure (CHF), myocardial infarction (MI) within six months of surgery, unstable angina, left ventricular hypertrophy (LVH), age >/= 65 years, male gender, current smoking, diabetes mellitus, hypertension, increased serum cholesterol and peripheral vascular disease (PVD) (Table 1).

Recently, another very important risk factor has been identified: postoperative myocardial ischemia. Mangano et al. demonstrated that the occurrence of postoperative myocardial ischemia within the first two days of surgery implies a nine-fold increase in risk for perioperative in-hospital cardiac complications (death, MI, unstable angina) and a two-fold increase in risk during the subsequent two years^1,2.

In the January 1998 issue of Anesthesiology, Wallace et al reveal that the simple intervention of perioperative beta-blockade can significantly decrease the incidence of postoperative myocardial ischemia, and reduce mortality during the two years following surgery.

In a placebo-controlled double-blind study they enrolled 200 patients undergoing noncardiac surgery with general anesthesia, who had the following cardiac risk factors: previous MI, angina, current or past surgery for PVD, male gender and two or more of: age >/= 65 years, hypertension, smoking, serum cholesterol >/= 240 mg/dL and diabetes mellitus. Exclusion factors included presence of left bundle branch block, a pacemaker, resting ST-T changes on ECG; CHF, complete heart block or bronchospasm. Patients were randomized to receive intravenous atenolol 10 mg (if the heart rate was >65 beats/min), 5 mg (heart rate 55-65 beats/min), 0 mg (heart rate <55 beats/min), or placebo. The drug was dosed preinduction, and then every 12 hours until the seventh postoperative day. When patients were able to eat, atenolol was given po in doses of 100 mg, 50 mg and 0 mg respectively. The drug was also withheld if systolic blood pressure was less than 100 mmHg.

Patients were monitored with 12-lead ECG and Holter ECG and blood levels were drawn for CPK-MB, 24 hours before and for seven days after surgery. ECG evidence of ischemia was defined as a reversible change in ST> 0.1 mV from baseline.

Patients who received atenolol had a significant slowing of heart rate in the perioperative period and a striking reduction in the incidence of myocardial ischemia. The mean intraoperative heart rate was < 50 beats/min in 38% of atenolol patients vs 15% of controls, and over 100 beats/min in 35% of atenolol patients vs 54% of controls. The mean postoperative heart rate was 75 beats/min (range, 50-113) in the atenolol patients vs 87 beats/min (range, 59-130) in the controls. During the first two postoperative days, the incidence of myocardial ischemia was 17% with atenolol, and 34% without it; in the first week postoperatively, it was 24% with atenolol, and 39% without it. All these differences were highly statistically significant. However, the study did not have the power to discriminate between the two groups with respect to in-hospital unstable angina, MI or death.

Patients who had postoperative ischemic episodes were more likely to die in the next two years. Of the 39% of patients who developed postoperative ischemia, 26% died; of the 61% who did not, only 13% died in the subsequent two years.

There were no differences in the safety endpoint criteria of hypotension, bradycardia or bronchospasm. The authors concluded that administration of perioperative beta-blockade significantly decreases the incidence of postoperative myocardial ischemia and the risk of death within two years after surgery. Moreover, it can be accomplished with minimal adverse effects attributable to beta-blockade, such as hypotension, bradycardia or bronchospasm.

In an accompanying editorial, Dr David Warltier of the Medical College of Wisconsin describes beta-blockers as being "incredibly useful, incredibly under-utilized", and urges greater perioperative use of these agents in patients undergoing surgery who have cardiac risk factors.

In conclusion, it is incumbent upon all anesthesiologists and anesthetists to be aware of the prognostic importance of postoperative myocardial ischemia, and to understand that it can be significantly reduced by the simple expedient of perioperative beta-blockade.

Table 1: Risk Factors for Perioperative Myocardial Ischemia

congestive heart failure

myocardial infarction within six months of surgery

unstable angina

left ventricular hypertrophy (LVH)

age >= 65 years

male gender

current smoking

diabetes mellitus

hypertension

increased serum cholesterol

peripheral vascular disease

¹ Longterm cardiac prognosis following noncardiac surgery. Mangano DT, Browner WS, Hollenberg M, Li J, Tateo IM; JAMA 1992;268:233-9

² Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. Mangano DT, Browner WS, Hollenberg M, London MJ, Tubau JF, Tateo IM.; N Engl J Med 1990; 323:1781-8.

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ABSTRACT