0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Scientific Review and Clinical Applications |

β-Blockers and Reduction of Cardiac Events in Noncardiac Surgery:  Scientific Review FREE

Andrew D. Auerbach, MD, MPH; Lee Goldman, MD
[+] Author Affiliations

Author Affiliations: Department of Medicine, University of California–San Francisco.


JAMA. 2002;287(11):1435-1444. doi:10.1001/jama.287.11.1435.
Text Size: A A A
Published online

Context Recent studies suggest that perioperatively administered β-blockers may reduce the risk of adverse cardiac events in patients undergoing major noncardiac surgery.

Objective To review the efficacy of perioperative β-blockade in reducing myocardial ischemia, myocardial infarction, and cardiac or all-cause mortality from randomized trials.

Data Sources A MEDLINE and conventional search of English-language articles published since 1980 was performed to gather information related to perioperative cardiac complications and β-blockade. Reference lists from all relevant articles and published recommendations for perioperative cardiac risk management were reviewed to identify additional studies.

Study Selection and Data Extraction Prospective randomized studies (6) were included in the analysis if they discussed the impact of β-blockade on perioperative cardiac ischemia, myocardial infarction, and mortality for patients undergoing major noncardiac surgery. Articles were examined for elements of trial design, treatment protocols, important biases, and major findings. These elements were then qualitatively compared.

Data Synthesis We identified 5 randomized controlled trials: 4 assessed myocardial ischemia and 3 reported myocardial infarction, cardiac, or all-cause mortality. All studies sought to achieve β-blockade before the induction of anesthesia by titrating doses to a target heart rate. Of studies reporting myocardial ischemia, numbers needed to treat were modest (2.5-6.7). Similarly modest numbers needed to treat were observed in studies reporting a significant impact on cardiac or all-cause mortality (3.2-8.3). The most marked effects were seen in patients at high risk; the sole study reporting a nonsignificant result enrolled patients with low baseline risk. As a group, studies of perioperative β-blockade have enrolled relatively few carefully selected patients. In addition, differences in treatment protocols leave questions unanswered regarding optimal duration of therapy.

Conclusions Despite heterogeneity of trials, a growing literature suggests a benefit of β-blockade in preventing perioperative cardiac morbidity. Evidence from these trials can be used to formulate an effective clinical approach while definitive trials are awaited.

Figures in this Article

Cardiac events such as myocardial infarction or cardiac death are common complications of surgery, occurring in 1% to 5% of unselected patients undergoing noncardiac surgery.16 These events are associated with markedly increased mortality7,8 and result in higher costs,6,9 making them the most common reasons for preoperative evaluations.1012

The prevalence of these events and their high mortality have made the prevention of perioperative cardiac events the subject of practice guidelines,13 position papers,14 and numerous prediction rules seeking to identify patients at high risk for cardiac complications.5,7,1520 Until recently, attempts to reduce the incidence of these complications depended on preoperative assessments of risk followed by clinical recommendations, including the option of postponing or canceling the surgical procedure.13,14

The evidence behind guidelines for testing or interventions, whether preoperative, intraoperative, or postoperative, was remarkably weak even as consensus approaches were developed for using treatments up to and including prophylactic coronary artery bypass surgery. Concern exists that preoperative intervention might prove detrimental because it remains unclear whether the benefit in reduced perioperative cardiac events is offset by the risks of revascularization itself.13,14,21,22 Strategies including percutaneous transluminal angioplasty as the revascularization modality are promising23; large prospective trials examining these approaches are under way.

Strong evidence links myocardial ischemia with postoperative cardiac events.2428 One study found that postoperative ischemia increased the odds of postoperative myocardial events 21-fold.29 As a result, medical strategies to reduce perioperative ischemia have been proposed. Studies using intraoperative calcium channel blockers30,31 or intravenous nitroglycerin32,33 provided mixed results. In contrast, small observational studies of β-blocking agents were more promising, with several suggesting that β-adrenoreceptor blockade blunted electrocardiographic signs of ischemia.3436 Extending this observation, several recent randomized trials have examined the effects of perioperative β-blocker administration on patient outcomes, including perioperative ischemia, myocardial infarction, and mortality. Results of these investigations may describe an important new method of reducing perioperative cardiac risk.

The details of our literature search methods have been described previously.37 Studies were identified by searching the MEDLINE electronic bibliographic database. The search strategy was performed by using the Medical Subject Heading (MeSH) terms perioperative care, postoperative complications, adrenergic antagonists, adrenergic β-antagonists, myocardial ischemia, myocardial infarction, mortality, and heart disease mortality. In addition, we searched for key title words related to perioperative cardiac complications and adrenergic blockade and combined the results of these searches with MeSH terms. Reference lists from all relevant articles and published recommendations for perioperative cardiac risk management13,14,38 were reviewed to identify additional studies.

To account for advances in perioperative medical, surgical, and anesthetic technique, we limited our search to investigations published since 1980. To focus on efficacy, we further limited our search to prospective randomized trials reporting the impact of β-blockade on perioperative cardiac ischemia, myocardial infarction, and mortality.

Because of the recognized difficulties in quality scoring of randomized trials,39,40 we did not score the quality of trials meeting our inclusion criteria. However, the abstraction forms for each trial did include key elements pertaining to trial design, such as blinding, comparability of the intervention and control groups, completeness of follow-up, and important confounders or biases.

Our search strategy yielded 7 randomized trials of perioperative β-blockade. A randomized trial by Harwood et al41 was excluded because both groups received β-blockers (ie, there was no control group). Although data from a study by Wallace et al26 were derived from the study by Mangano et al,42 the study reported effects of β-blockade on different outcomes (ie, myocardial ischemia) and was included as a subset of the same study in our review.

Thus, this review included 6 publications representing 5 trials studying the effectiveness of perioperative β-blockade in reducing perioperative myocardial ischemia and cardiac or all-cause mortality (Table 1).

Table Graphic Jump LocationTable. Randomized Controlled Trials of the Effectiveness of Perioperative β-Blockade*

Although studies used different agents, doses, and dosing schedules, the general approach in each study was similar: administration of a β-blocker before induction of anesthesia, followed by β-blockade throughout the operation and postoperative period. In all but one study, the dose was titrated to a target heart rate, generally 70/min or lower (Table 1).

The identified studies reported a range of clinical outcomes: 4 included assessment of myocardial ischemia,26,36,43,44 and 3 reported myocardial infarction, pulmonary edema, cardiac death, or all-cause mortality.42,44,45

Of 4 studies reporting the effect of β-blockers on perioperative ischemia, all but 1 found a statistically significant reduction in ischemia among treated patients. Wallace et al,26 in a subset analysis of data from Mangano et al,46 reported less frequent perioperative myocardial ischemia in atenolol-treated patients. Stone et al43 suggested a similar effect of β-blockade on Holter monitor–documented myocardial ischemia. However, the authors did not report the types of procedures included in their sample, nor did they statistically compare baseline patient characteristics, leaving their conclusions open to debate. Raby et al36 also found a significant beneficial effect of β-blockade by using a continuous infusion of esmolol in high-risk patients undergoing vascular surgery. Although Urban et al44 also found a reduction in perioperative ischemia, this difference failed to reach statistical significance. These findings may be explained in part by differences in the cardiac risk of this cohort, who were undergoing elective total knee replacement. In studies finding a statistical difference, rates of ischemia were between 28% and 73% in controls compared with the 15% rate of ischemia observed in this control group. In addition, the target heart rate of 80/min used in this study was substantially higher than that in other studies, suggesting that inadequate adrenergic blockade may have played a role in their findings.

Of studies reporting cardiac events and cardiac mortality, 2 reported significant improvement in patient outcomes because of β-blockade. In a study of male veterans at risk for coronary disease (BOX 1) and undergoing major noncardiac surgery, Mangano et al42 observed no difference in in-hospital mortality caused by β-blockade. However, they observed a relative reduction in all-cause mortality of nearly 55% at 2 years. This difference, which appeared within the first 8 months of follow-up, was ascribed to a marked reduction in cardiac events in the first year of therapy (67% reduction at year 1, 48% at year 2). Patients in the β-blocker group had less coronary disease at study entry, were receiving angiotensin-converting enzyme inhibitors more frequently, and were less likely to have β-blocker use discontinued postoperatively, perhaps biasing results in favor of the treatment group.47,48 However, adjustment for these differences in multivariable models did not alter their findings.46 Although acknowledging the limitations of their results in terms of generalizability to other patient populations and sites, the authors favored broader use of β-blockade in clinical trials.

Box 1. Eligibility Criteria for Use of Perioperative β-Blockers

Minor Clinical Criteria (Adapted From Mangano et al42)
Use β-blockers in patients meeting any 2 of the following criteria:
 Aged 65 years or older
 Hypertension
 Current smoker
 Serum cholesterol concentration at least 240 mg/dL (6.2 mmol/L)
 Diabetes mellitus not requiring insulin therapy

Revised Cardiac Risk Index Criteria5*
Use β-blockers in patients meeting any of the following criteria:
High-risk surgical procedure, defined as intraperitoneal, intrathoracic, or suprainguinal vascular procedure
 Ischemic heart disease, defined as the following:
 History of myocardial infarction
 History of or current angina
 Use of sublingual nitroglycerine
 Positive exercise test results
 Q waves on electrocardiogram
 Patients who have undergone percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery and who have chest pain presumed to be of ischemic origin
Cerebrovascular disease, defined as the following:
 History of transient ischemic attack
 History of cerebrovascular accident
Diabetes mellitus requiring insulin therapy
Chronic renal insufficiency, defined as a baseline creatinine level of at least 2.0 mg/dL (177 µmol/L)

*Suggested by Boersma et al.60 Congestive heart failure is also an element in the Revised Cardiac Risk Index but is not an indication for perioperative β-blockade.

Poldermans et al45 found an even greater benefit of β-blockade among high-risk patients. These investigators enrolled patients who were to undergo vascular surgery and had myocardial ischemia documented by dobutamine echocardiography, with an estimated rate of major perioperative cardiac events of 28%. The entire patient cohort had experienced a 90% reduction in cardiac death or nonfatal myocardial infarction by 30 days. Follow-up care did not include additional therapy (ie, cardiac catheterization or revascularization), raising concerns that the research algorithm did not realistically reflect clinical practice.49,50 However, if the true rate of events in β-blocker–treated patients is low (the point estimate from this small study was 3.4%), the risks associated with revascularization51 may outweigh any incremental benefit.

In contrast to the previous 2 studies, the study by Urban et al44 found no significant difference in rates of in-hospital myocardial infarction. It is likely that these investigators' ability to detect a difference was limited in part by the relatively small sample size and shorter length of follow-up. This study also included a large proportion of patients (30% in each group) who had been receiving β-blockers preoperatively; such patients were variably excluded from other trials. Patients who are β-blocker naive may have a different response to perioperative β-blockers, or long-term use of these agents may represent a confounding factor incompletely accounted for in other studies of perioperative β-blockade.

Differences in absolute magnitude of benefit can be ascribed in part to the cardiac risks of the patients enrolled (reflected in event rates in the control groups), with the greatest absolute benefits seen in patients at highest risk. That is, assuming a fixed relative benefit of β-blockade, the absolute differences in rates of adverse events will vary according to the baseline risk of the patients treated. For patients at extremely high risk, such as those enrolled by Poldermans et al,45 the absolute reduction in risk was 30%, resulting in a number needed to treat of slightly more than 3. In contrast, Mangano et al42 observed an 8% absolute risk reduction, suggesting that 9 patients would require therapy to reduce mortality at 2 years. Although not statistically significant, the 4% absolute reduction in risk (2% in treated patients vs 6% in control patients) observed by Urban et al44 would result in a much larger number needed to treat, despite an approximately 33% reduction in risk.

Stone et al43 reported high rates of bradycardia (21 of 89 patients) in β-blocker–treated patients, half of whom required atropine therapy. Adverse events related to the use of β-blockers in other reviewed studies were similarly infrequent. For example, 38% of β-blocker–treated subjects, compared with 15% of control subjects, had bradycardia intraoperatively, but other postoperative adverse events were rare and did not require discontinuation of the medication.42 Similar rates of adverse effects have been noted in studies examining β-blockade in patients undergoing cardiac surgery.41,52,53 One study examining the use of propranolol in patients undergoing thoracotomy for pneumonectomy suggested that patients receiving this nonselective β-blocker had more frequent postoperative bradycardia (25% vs 4%; P = .018) and hypotension (49% vs 20%; P = .003); higher incidence of pulmonary edema (16% vs 8%; P = .45) was not statistically significant.54

The use of perioperative β-blockade in patients who had not been receiving β-blockers long-term may also pose an additional risk in that withdrawal of β-blockers may lead to adrenergic hypersensitivity and possibly worsen outcomes. A recent prospective observational study noted that patients who were not receiving β-blockers long-term but who discontinued perioperative use immediately after surgery had a markedly increased risk for postoperative myocardial infarction.55 This effect was not observed in randomized trials of β-blockade that used shorter treatment regimens36,43 and needs to be confirmed by larger studies. Alternatively, confusion about the use of β-blockade or discontinuity in postoperative care may lead to β-blockers' being inappropriately discontinued during hospitalization or afterward. Discontinuing β-blocker use in patients who have a longstanding indication for adrenergic blockade may lead to adverse outcomes perioperatively56 or worsened patient survival.5759

Which Patients Should Receive β-Blockers Perioperatively?

Studies of perioperative β-blockade have been performed largely in selected patient populations with a risk of perioperative cardiac events that is higher, on average, than that of the general population of surgical patients. Thus, physicians must seek data from studies that included patients most akin to those they treat in practice. Although it has significant limitations, the study by Mangano et al46 is the only one to enroll a reasonably broad spectrum of surgical patients. Thus, its criteria may represent a reasonable means of identifying patients who would benefit from β-blockade (BOX 1), largely by excluding low-risk patients. This approach has been incorporated into the American College of Physicians guidelines.14

A recent observational study of patients undergoing vascular surgery suggested a clinical approach to the use of β-blockade. In this study, adjusted relative risk of postoperative cardiac events among patients receiving β-blockers was 0.3 (95% confidence interval [CI], 0.1-0.7) across strata of the Revised Cardiac Risk Index (BOX 1),60 an effect size similar to that seen in randomized trials. However, lowest-risk patients who had no Revised Cardiac Risk Index criteria received little benefit in absolute terms from β-blockers, while those at highest risk (3 or more criteria) remained at substantial risk even if treated with β-blockers. As an observational trial, these findings may be subject to confounding factors not accounted for in multivariable analyses and may not be generalizable to other groups.

The effectiveness of β-blockade in patients at high risk because of aortic stenosis or unstable or severe cardiovascular symptoms is unknown. It is likely that patients with severe cardiac symptoms caused by angina pectoris would benefit from β-blockade, but these patients have not been studied directly. The safety and effectiveness of new preoperative β-blockade in patients with a depressed ejection fraction is also unknown, since these patients were not included in randomized trials. β-Blockade has not been studied in patients undergoing regional anesthesia or conscious sedation. In addition, no study to date has directly examined the use of β-blockade in patients who have poor functional status and might otherwise be referred for additional noninvasive testing.8,13,14,61 Patients who are at risk because of high-grade conduction system disease have an absolute contraindication to β-blockade and require different management strategies.

The effectiveness of β-blockade in terms of costs or outcomes in patients at low risk is unclear. Results from Boersma et al60 suggest that β-blockade provides little additional benefit in patients with no clinical risk factors. Thus, it seems likely that patients who are undergoing low-risk procedures (eg, those undergoing same-day or outpatient surgery or ophthalmic surgery) and have no or minimal cardiac risk factors may be as likely to experience adverse effects from β-blockers as to experience a cardioprotective benefit.

β-Blockade may have additional beneficial effects for elderly patients. In one study, patients who received β-blockers were extubated more quickly, required less medication for pain, and were more alert sooner after surgery.62 Although the unblinded nature of this study leaves its findings open to debate, the possibility of additional benefits is tantalizing and worthy of further investigation.

Which β-Blocking Agent Should Be Used?

All studies showing benefit of β-blockade on mortality and myocardial ischemia have used β1-selective agents. Nonselective agents such as propranolol, although likely to have a similar impact on myocardial oxygen demand if titrated appropriately, are more likely to produce adverse pulmonary effects63,64 and in fact caused more bronchospasm in one study of perioperative propranolol.54

No evidence suggests an advantage of any particular β1-selective β-blocker. Studies to date have used several agents, suggesting that the efficacy of β-blockade is class rather than drug dependent. Blocking or blunting adrenergic responses is the key pathophysiologic step connecting β-blockers to improved outcomes, and evidence suggests that physicians may choose any medication that meets this physiologic goal.

Patients who are receiving long-term β-blocker therapy need not begin taking one of the drugs used in published studies instead. Evidence from Mangano et al42 and Urban et al44 support using additional intravenous agents, whether an additional dose of the patient's long-term medication or another β-blocker, immediately perioperatively, but no evidence supports exchanging one agent for another.

Are Other Adrenergic Blocking Agents Effective?

Selective sympatholytics (α2) may also improve patient outcomes. Clonidine has been suggested to lower blood pressure, heart rate, and norepinephrine levels in patients undergoing surgery, factors considered key in preventing myocardial ischemia.65,66 In fact, one study of 297 patients undergoing vascular surgery suggested that clonidine-treated patients had fewer episodes of ischemia.67 In a recent study, mivazerol, an α2-agonist that reduces postganglionic noradrenaline availability and spinal efferent sympathetic output, reduced the incidence of perioperative ischemia.68 A subsequent large randomized trial of 1897 patients undergoing noncardiac surgery produced mixed results, however.69 In the whole cohort, mivazerol had no statistically significant effect on all-cause mortality or myocardial infarction, but cardiac mortality was reduced by half (relative risk of events among treated patients, 0.50; 95% CI, 0.25-0.96). In planned subgroup analyses, a more marked impact was observed among patients undergoing vascular surgery, where the relative risk of postoperative myocardial infarction and death among treated patients was 0.67 (95% CI, 0.45-0.98), and the relative risk for cardiac death was 0.32 (95% CI, 0.12-0.76).69 Although mivazerol is not available in the United States, findings from this study support the central role of adrenergic blockade in preventing cardiac events.

No data to date suggest that α1-selective blocking agents provide any benefit to patients perioperatively, and use of these agents alone is not supported by current evidence. Patients receiving α1 blockers long-term would likely benefit from the addition of β-blocking agents perioperatively.

When Should β-Blocker Use Be Started Preoperatively and When Should It Be Discontinued?

Although questions remain regarding the optimal dosing schedule for perioperative β-blocker therapy, investigations showing a positive effect sought to achieve sympatholysis before induction of anesthesia. Thus, physicians should try to begin therapy early enough so that doses can be titrated appropriately. The time required to meet this goal may vary, depending on the agent, the route of administration, or patient factors, but it is clear that a physiologic dose of β-blocker must be administered for any positive impact to be appreciated. For example, intravenous atenolol, as used by Mangano et al,42 may be administered and titrated to a physiologic dose in the preanesthesia holding area or even the operating room. Physicians who choose to begin β-blocker therapy orally may require additional lead time for patients to reach the target heart rate. In fact, patients in Poldermans' study45 began oral therapy 1 month before surgery, on average, with titration of the dose performed at a visit 1 week after initiation of bisoprolol.

Postoperatively, most protocols extended beyond the first postoperative day and even up to 1 month after surgery. Nonrandomized data from Shammash et al55 and previous case reports suggest the hazards of discontinuation of β-blockers immediately postoperatively. A recent study suggested that, among vascular surgery patients who had not been receiving β-blockers long-term, continuing β-blockade up to 3 years after surgery reduced cardiac mortality.70 Although tantalizing, these results are based on a small number of patients (n = 112) with a high burden of cardiovascular illness and need to be reproduced in larger, less selected cohorts.

The safest conclusion to be drawn from current studies is that β-blocker use should begin before surgery, even up to a month before the procedure, with titration of the dose taking place as an outpatient procedure and up to the induction of anesthesia. Therapy should be continued at least through hospitalization, and longer if adequate medical follow-up can be arranged postoperatively. Close follow-up is particularly important in the care of patients who were not receiving β-blockers long-term before surgery so that the drug dose can be tapered if long-term use is not indicated. Follow-up is also imperative for patients receiving β-blockers for medical reasons so that continuity in their medication is maintained.

Ample evidence suggests that long-term β-blocker therapy is underused in patients with definitive indications.7177 Thus, the perioperative period may represent an opportunity to begin β-blocker therapy in appropriate patients, such as those with a history of myocardial infarction.

Long-term use of β-blockade for patients with heart failure has been clearly shown to improve patient mortality,78 and these patients might also be identified perioperatively. However, guidelines for administration of these agents in patients with heart failure require close monitoring,79 and the doses administered are usually far lower and not titrated to heart rate. β-Blockade in these patients, therefore, should not be routinely started for prophylaxis perioperatively.

In Which Patients Should Additional Cardiac Risk Stratification Be Pursued?

Data describing the effectiveness of β-blockade, especially the results of the study by Poldermans et al,45 have made some authors wonder whether risk stratification is still necessary.49 However, β-blockers alone may not reduce the risk of postoperative cardiac events below thresholds suggested in the American College of Physicians14 or American Heart Association/American College of Cardiology risk stratification guidelines.13 In the study by Boersma et al,60 patients who were in the highest risk strata (5 or more points according to the Revised Cardiac Risk Index of Lee et al)5 and received β-blockers continued to have an estimated cardiac event rate of 14%; these authors suggested that patients with more than 3 clinical predictors (3.4% rate of postoperative cardiac events) be referred for additional risk stratification using noninvasive testing. Thus, although β-blockade may increase the threshold at which physicians refer patients for additional testing, the era of risk stratification is not over.

Although the literature to date has gaps and areas of uncertainty, there is ample evidence to suggest a clinical approach to the patient undergoing elective surgery. We have synthesized the results of our literature review into a clinical algorithm (Figure 1), a set of patient selection criteria (BOX 1), and a list of suggested medications, routes, and dosages (BOX 2).

Box 2. Perioperative β-Blockers: Agents and Regimens

Prehospitalization (Outpatients) or Immediately Following Admission to Hospital
Not taking β-blockers long-term
 Atenolol, 50-100 mg, perioperatively every day42 or bisoprolol, 5-10 mg, perioperatively every day45
 Begin as outpatient up to 30 days before surgery
 Titrate to heart rate of ≤65/min
Taking β-blockers long-term
 Continue long-term therapy
 Titrate heart rate to ≤65/min, if needed

Immediate Postoperative Period (ie, in Preanesthesia Holding Area)
Atenolol, 5-10 mg, intravenously to reach target heart rate before introduction of anesthesia, if needed,42 whether β-blockers are taken long-term or not

Immediate Postoperative Period and Transition to Oral Medications, Whether β-Blockers Are Taken Long-term or Not
Patient not taking oral medications and hemodynamically stable
 Atenolol, 5-10 mg, intravenously twice daily to target heart rate42
Patient unstable, eg, high bleeding risk or in the intensive care unit
 Esmolol, 500 µg/kg, intravenously for 1 minute and then infusion of 50-200 µg/kg per minute to target heart rate37,43
Patient taking oral medications
 Resume perioperative β-blocker use at previous dose; titrate as necessary to target heart rate
 Overlap first oral dose with continued intravenous agents to maintain target heart rate, if necessary.

Figure. Perioperative β-Blockers: Patient Selection and Preoperative Risk Stratification
Graphic Jump Location
Revised Cardiac Risk Index criteria5 and minor clinical criteria adapted from Mangano et al42 are listed in Table 2. Revised Cardiac Risk Index criteria exclude patients with congestive heart failure because the safety and efficacy of perioperative β-blockers has not been proven in these patients. Cardiac event rates with and without β-blockade are ranges based on rates from Lee et al5 for cardiovascular complications observed in the validation set (those in the derivation set were somewhat lower) and on estimates from Boersma et al.60 Options for noninvasive testing for further risk stratification include dipyramidole thallium scintigraphy, stress echocardiography, exercise electrocardiography, or cardiac catheterization in appropriate patients. Examples of activities that expend about 4 METS (metabolic equivalent tasks) include climbing 1 flight of stairs, being able to walk on level ground at 4 mph, or being able to climb a short hill without difficulty.

As in the era before β-blockers, the initial approach to the patient should include risk stratification according to clinical criteria. As described, there are numerous risk stratification strategies available to physicians, many of which have published information regarding test characteristics and accuracy. There is little reason to suspect that other risk indices could not be used similarly, but only 1 study has explicitly reported the use of any risk-stratification method in the context of β-blocker use.60 This study used the Revised Cardiac Risk Index of Lee et al5 to identify high-, intermediate-, and low-risk groups and suggested a strategy for further testing or use of β-blockers. The criteria of Mangano et al42 provide an alternative approach to choosing patients, largely by excluding patients at lowest risk, but do not identify patients who require further risk stratification alone.

The first step in risk stratification is to identify patients who are at lowest risk (those whose estimated risk for perioperative cardiac events is less than 1% without β-blockers) and those at highest risk (those whose estimated risk is higher than 10%). Using β-blockers in patients at low risk (0 Revised Cardiac Risk Index criteria and none of the cardiac risk factors in Mangano et al42; BOX 1) imparts little absolute benefit, and surgery can proceed without addition of this medication. In contrast, patients at highest risk (3 or more Revised Cardiac Risk Index criteria) require additional risk stratification using noninvasive or invasive testing. Although the study by Boersma et al60 used dobutamine echocardiography to identify highest-risk patients, other noninvasive testing and even coronary angiography may be substituted according to published guidelines.13 As described, the utility of preoperative revascularization remains unclear, except in patients with an indication for these procedures in the absence of the planned surgical procedure. We recommend noninvasive testing only in higher-risk patients and in moderate-risk patients whose exercise capacity cannot be determined by history, a much narrower use of testing than recommended by some80 but consistent with the recommendations of others.13,14

Patients who are at high risk and have negative noninvasive testing results and those at intermediate risk (1-2 Revised Cardiac Risk Index criteria) should begin taking a β-blocker if not taking one long-term (BOX 2). Optimally, medications should be started before hospitalization and, if possible, as long as 30 days before surgery. This period, used in the study by Poldermans et al,45 will allow for adequate titration of the medication to the target heart rate. Patients receiving β-blockers long-term should have their dose evaluated and adjusted appropriately as outpatients. Dose titration up to induction of anesthesia may be performed with intravenous atenolol38 in all patients.

Postoperatively, oral β-blocker use should be restarted as soon as possible, with intravenous atenolol42 used for stable patients who are unable to take medications orally. Patients who are unstable should receive a short-acting intravenous β-blocker such as esmolol until they are able to tolerate longer-acting oral medications. The transition to oral medications should overlap with intravenous medications to maintain a target heart rate. Oral β-blocker use should be continued at least through hospitalization and up to 1 month postoperatively, when a gradual reduction in the dose can be initiated in patients without an indication for long-term therapy. As mentioned, the postoperative visit may also represent an opportunity to begin long-term β-blocker therapy in appropriate patients.

Results from several well-designed clinical trials suggest that use of β-blockers perioperatively is associated with significant reductions in cardiac morbidity and mortality. However, as a group, studies that support their use are relatively small, with a total enrollment of fewer than 700 patients. In addition, these studies often included patients who were selected and not consecutively recruited, making generalizability of their results difficult. No randomized study to date has compared the impact of β-blockade in an unselected population of patients undergoing surgery, so there is little direct evidence describing the impact of β-blockers in average patients, such as those who have stable coronary disease and are undergoing elective surgery. β-Blocker therapy may reduce the need for additional tests and revascularization procedures,8 further reducing costs of care, but wider use of this therapy will be better supported if findings from existing studies are replicated in large randomized trials. Studies are also required to answer questions regarding optimal duration of therapy, identify populations of patients in which β-blocker use is cost-effective, and allow for development of new perioperative risk-management algorithms that reflect the impact of β-blockers on patient outcomes.

Browner WS, Li J, Mangano DT. In-hospital and long-term mortality in male veterans following noncardiac surgery: the Study of Perioperative Ischemia Research Group.  JAMA.1992;268:228-232.
Ashton CM, Petersen NJ, Wray NP.  et al.  The incidence of perioperative myocardial infarction in men undergoing noncardiac surgery.  Ann Intern Med.1993;118:504-510.
Gilbert K, Larocque BJ, Patrick LT. Prospective evaluation of cardiac risk indices for patients undergoing noncardiac surgery.  Ann Intern Med.2000;133:356-359.
Khuri SF, Daley J, Henderson W.  et al.  The National Veterans Administration Surgical Risk Study: risk adjustment for the comparative assessment of the quality of surgical care.  J Am Coll Surg.1995;180:519-531.
Lee TH, Marcantonio ER, Mangione CM.  et al.  Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery.  Circulation.1999;100:1043-1049.
Lawrence VA, Hilsenbeck SG, Mulrow CD, Dhanda R, Sapp J, Page CP. Incidence and hospital stay for cardiac and pulmonary complications after abdominal surgery.  J Gen Intern Med.1995;10:671-678.
Goldman L. Multifactorial index of cardiac risk in noncardiac surgery: ten-year status report.  J Cardiothorac Anesth.1987;1:237-244.
Lee TH. Reducing cardiac risk in noncardiac surgery.  N Engl J Med.1999;341:1838-1840.
Collins TC, Daley J, Henderson WH, Khuri SF. Risk factors for prolonged length of stay after major elective surgery.  Ann Surg.1999;230:251-259.
Belzberg H, Rivkind AI. Preoperative cardiac preparation.  Chest.1999;115(5 suppl):82S-95S.
Merli GJ, Weitz HH. The medical consultant.  Med Clin North Am.1987;71:353-355.
Merli GJ, Weitz HH. Approaching the surgical patient: role of the medical consultant.  Clin Chest Med.1993;14:205-210.
Eagle KA, Berger PB, Calkins H.  et al.  ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [American College of Cardiology Web site]. Available at: http://www.acc.org/clinical/guidelines/perio/update/pdf/perio_update.pdf. Accessibility verified February 19, 2002.
American College of Physicians.  Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery.  Ann Intern Med.1997;127:309-312.
Detsky AS, Abrams HB, Forbath N, Scott JG, Hilliard JR. Cardiac assessment for patients undergoing noncardiac surgery: a multifactorial clinical risk index.  Arch Intern Med.1986;146:2131-2134.
L'Italien GJ, Paul SD, Hendel RC.  et al.  Development and validation of a Bayesian model for perioperative cardiac risk assessment in a cohort of 1081 vascular surgical candidates.  J Am Coll Cardiol.1996;27:779-786.
Steyerberg EW, Kievit J, de Mol Van Otterloo JC, van Bockel JH, Eijkemans MJ, Habbema JD. Perioperative mortality of elective abdominal aortic aneurysm surgery: a clinical prediction rule based on literature and individual patient data.  Arch Intern Med.1995;155:1998-2004.
Miller K, Atzenhofer K, Gerber G, Reichel M. Risk prediction in operatively treated fractures of the hip.  Clin Orthop.1993;293:148-152.
Jivegard L, Bergqvist D, Holm J.  et al.  Preoperative assessment of the risk for cardiac death following thrombo-embolectomy for acute lower limb ischaemia.  Eur J Vasc Surg.1992;6:83-88.
Larsen SF, Olesen KH, Jacobsen E.  et al.  Prediction of cardiac risk in non-cardiac surgery.  Eur Heart J.1987;8:179-185.
Eagle KA, Rihal CS, Mickel MC, Holmes DR, Foster ED, Gersh BJ.and the CASS Investigators and University of Michigan Heart Care Program.  Cardiac risk of noncardiac surgery: influence of coronary disease and type of surgery in 3368 operations: Coronary Artery Surgery Study.  Circulation.1997;96:1882-1887.
Foster ED, Davis KB, Carpenter JA, Abele S, Fray D. Risk of noncardiac operation in patients with defined coronary disease: the Coronary Artery Surgery Study (CASS) registry experience.  Ann Thorac Surg.1986;41:42-50.
Hassan SA, Hlatky MA, Boothroyd DB.  et al.  Outcomes of noncardiac surgery after coronary bypass surgery or coronary angioplasty in the Bypass Angioplasty Revascularization Investigation (BARI).  Am J Med.2001;110:260-266.
Reich DL, Bodian CA, Krol M, Kuroda M, Osinski T, Thys DM. Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery.  Anesth Analg.1999;89:814-822.
Hewer I, Drew B, Karp K, Stotts N. The utilization of automated ST segment analysis in the determination of myocardial ischemia.  AANA J.1997;65:351-356.
Wallace A, Layug B, Tateo I.  et al.  Prophylactic atenolol reduces postoperative myocardial ischemia: McSPI Research Group.  Anesthesiology.1998;88:7-17.
Raby KE, Barry J, Creager MA, Cook EF, Weisberg MC, Goldman L. Detection and significance of intraoperative and postoperative myocardial ischemia in peripheral vascular surgery.  JAMA.1992;268:222-227.
Mangano DT, Hollenberg M, Fegert G.  et al. and the Study of Perioperative Ischemia (SPI) Research Group.  Perioperative myocardial ischemia in patients undergoing noncardiac surgery, I: incidence and severity during the 4 day perioperative period.  J Am Coll Cardiol.1991;17:843-850.
Landesberg G, Luria MH, Cotev S.  et al.  Importance of long-duration postoperative ST-segment depression in cardiac morbidity after vascular surgery.  Lancet.1993;341:715-719.
Godet G, Coriat P, Baron JF.  et al.  Prevention of intraoperative myocardial ischemia during noncardiac surgery with intravenous diltiazem: a randomized trial versus placebo.  Anesthesiology.1987;66:241-245.
Antunes E, Serra J, Ferreira R.  et al.  Effects of diltiazem on myocardial ischemia in patients with coronary artery disease.  Rev Port Cardiol.1993;12:219-223.
Coriat P. Intravenous nitroglycerin dosage to prevent intraoperative myocardial ischemia during noncardiac surgery.  Anesthesiology.1986;64:409-410.
Dodds TM, Stone JG, Coromilas J, Weinberger M, Levy DG. Prophylactic nitroglycerin infusion during noncardiac surgery does not reduce perioperative ischemia.  Anesth Analg.1993;76:705-713.
Smulyan H, Weinberg SE, Howanitz PJ. Continuous propranolol infusion following abdominal surgery.  JAMA.1982;247:2539-2542.
Pasternack PF, Grossi EA, Baumann FG.  et al.  Beta blockade to decrease silent myocardial ischemia during peripheral vascular surgery.  Am J Surg.1989;158:113-116.
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;88:477-482.
Shojania KG, Duncan BW, McDonald KM, Wachter RM. Making Health Care Safer: A Critical Analysis of Patient Safety Practices: Evidence Report/Technology Assessment No. 43. Rockville, Md: Agency for Healthcare Research and Quality; 2001. Publication 01-E058.
Mangano DT, Goldman L. Preoperative assessment of patients with known or suspected coronary disease.  N Engl J Med.1995;333:1750-1756.
Juni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials.  BMJ.2001;323:42-46.
Juni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials for meta-analysis.  JAMA.1999;282:1054-1060.
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;13:555-561.
Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery: Multicenter Study of Perioperative Ischemia Research Group.  N Engl J Med.1996;335:1713-1720.
Stone JG, Foex P, Sear JW, Johnson LL, Khambatta HJ, Triner L. Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent.  Anesthesiology.1988;68:495-500.
Urban MK, Markowitz SM, Gordon MA, Urquhart BL, Kligfield P. Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia.  Anesth Analg.2000;90:1257-1261.
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;341:1789-1794.
Mangano DT. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.  N Engl J Med.1997;336:1452.
Reis SE, Feldman AH. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.  N Engl J Med.1997;336:1453.
Petros JA. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.  N Engl J Med.1997;336:1452.
Litwack RS, Gilligan DM, DeGruttola V. Beta-blockade for patients undergoing vascular surgery.  N Engl J Med.2000;342:1052.
Feldman T, Fusman B, Mckinsey JF. Beta-blockade for patients undergoing vascular surgery.  N Engl J Med.2000;342:1051-1052.
Poldermans D, Boersma E. Beta-blockade for patients undergoing vascular surgery.  N Engl J Med.2000;342:1052-1053.
Hammon Jr JW, Wood AJ, Prager RL, Wood M, Muirhead J, Bender Jr HW. Perioperative beta blockade with propranolol: reduction in myocardial oxygen demands and incidence of atrial and ventricular arrhythmias.  Ann Thorac Surg.1984;38:363-367.
Lamb RK, Prabhakar G, Thorpe JA, Smith S, Norton R, Dyde JA. The use of atenolol in the prevention of supraventricular arrhythmias following coronary artery surgery.  Eur Heart J.1988;9:32-36.
Bayliff CD, Massel DR, Inculet RI.  et al.  Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery.  Ann Thorac Surg.1999;67:182-186.
Shammash JB, Trost JC, Gold JM, Berlin JA, Golden MA, Kimmel SE. Perioperative beta-blocker withdrawal and mortality in vascular surgical patients.  Am Heart J.2001;141:148-153.
Goldman L. Noncardiac surgery in patients receiving propranolol: case reports and recommended approach.  Arch Intern Med.1981;141:193-196.
Gilligan DM, Chan WL, Stewart R, Oakley CM. Adrenergic hypersensitivity after beta-blocker withdrawal in hypertrophic cardiomyopathy.  Am J Cardiol.1991;68:766-772.
Swedberg K, Hjalmarson A, Waagstein F, Wallentin I. Adverse effects of beta-blockade withdrawal in patients with congestive cardiomyopathy.  Br Heart J.1980;44:134-142.
Miller RR, Olson HG, Amsterdam EA, Mason DT. Propranolol-withdrawal rebound phenomenon: exacerbation of coronary events after abrupt cessation of antianginal therapy.  N Engl J Med.1975;293:416-418.
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;285:1865-1873.
Goldman L. Assessing and reducing cardiac risks of noncardiac surgery.  Am J Med.2001;110:320-323.
Zaugg M, Tagliente T, Lucchinetti E.  et al.  Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery.  Anesthesiology.1999;91:1674-1686.
Fallowfield JM, Marlow HF. Propranolol is contraindicated in asthma.  BMJ.1996;313:1486.
van Zyl AI, Jennings AA, Bateman ED, Opie LH. Comparison of respiratory effects of two cardioselective beta-blockers, celiprolol and atenolol, in asthmatics with mild to moderate hypertension.  Chest.1989;95:209-213.
Ellis JE, Drijvers G, Pedlow S.  et al.  Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.  Anesth Analg.1994;79:1133-1140.
Quintin L, Bouilloc X, Butin E.  et al.  Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study.  Anesth Analg.1996;83:687-695.
Stuhmeier KD, Mainzer B, Cierpka J, Sandmann W, Tarnow J. Small, oral dose of clonidine reduces the incidence of intraoperative myocardial ischemia in patients having vascular surgery.  Anesthesiology.1996;85:706-712.
Fox K, Dargie HJ, de Bono DP, Oliver MF, Wulfert E, Kharkevitch T. Effect of an alpha(2) agonist (mivazerol) on limiting myocardial ischaemia in stable angina.  Heart.1999;82:383-385.
Oliver MF, Goldman L, Julian DG, Holme I. Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease: the European Mivazerol Trial (EMIT).  Anesthesiology.1999;91:951-961.
Poldermans D, Boersma E, Bax JJ.  et al.  Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery.  Eur Heart J.2001;22:1353-1358.
Krumholz HM, Radford MJ, Wang Y, Chen J, Marciniak TA. Early beta-blocker therapy for acute myocardial infarction in elderly patients.  Ann Intern Med.1999;131:648-654.
Krumholz HM, Radford MJ, Wang Y, Chen J, Heiat A, Marciniak TA. National use and effectiveness of beta-blockers for the treatment of elderly patients after acute myocardial infarction: National Cooperative Cardiovascular Project.  JAMA.1998;280:623-629.
White CM. Prevention of suboptimal beta-blocker treatment in patients with myocardial infarction.  Ann Pharmacother.1999;33:1063-1072.
Wang TJ, Stafford RS. National patterns and predictors of beta-blocker use in patients with coronary artery disease.  Arch Intern Med.1998;158:1901-1906.
Soumerai SB, McLaughlin TJ, Spiegelman D, Hertzmark E, Thibault G, Goldman L. Adverse outcomes of underuse of beta-blockers in elderly survivors of acute myocardial infarction.  JAMA.1997;277:115-121.
Radford MJ, Krumholz HM. Beta-blockers after myocardial infarction—for few patients, or many?  N Engl J Med.1998;339:551-553.
Gurwitz JH, Goldberg RJ, Chen Z, Gore JM, Alpert JS. Beta-blocker therapy in acute myocardial infarction: evidence for underutilization in the elderly.  Am J Med.1992;93:605-610.
Packer M. Current role of beta-adrenergic blockers in the management of chronic heart failure.  Am J Med.2001;110:81S-94S.
Heart Failure Society of America.  HFSA guidelines for management of patients with heart failure caused by left ventricular systolic dysfunction: pharmacological approaches.  Pharmacotherapy.2000;20:495-522.
Fleisher LA, Eagle KA. Lowering cardiac risk in noncardiac surgery.  N Engl J Med.2001;345:1677-1682.

Figures

Figure. Perioperative β-Blockers: Patient Selection and Preoperative Risk Stratification
Graphic Jump Location
Revised Cardiac Risk Index criteria5 and minor clinical criteria adapted from Mangano et al42 are listed in Table 2. Revised Cardiac Risk Index criteria exclude patients with congestive heart failure because the safety and efficacy of perioperative β-blockers has not been proven in these patients. Cardiac event rates with and without β-blockade are ranges based on rates from Lee et al5 for cardiovascular complications observed in the validation set (those in the derivation set were somewhat lower) and on estimates from Boersma et al.60 Options for noninvasive testing for further risk stratification include dipyramidole thallium scintigraphy, stress echocardiography, exercise electrocardiography, or cardiac catheterization in appropriate patients. Examples of activities that expend about 4 METS (metabolic equivalent tasks) include climbing 1 flight of stairs, being able to walk on level ground at 4 mph, or being able to climb a short hill without difficulty.

Tables

Table Graphic Jump LocationTable. Randomized Controlled Trials of the Effectiveness of Perioperative β-Blockade*

References

Browner WS, Li J, Mangano DT. In-hospital and long-term mortality in male veterans following noncardiac surgery: the Study of Perioperative Ischemia Research Group.  JAMA.1992;268:228-232.
Ashton CM, Petersen NJ, Wray NP.  et al.  The incidence of perioperative myocardial infarction in men undergoing noncardiac surgery.  Ann Intern Med.1993;118:504-510.
Gilbert K, Larocque BJ, Patrick LT. Prospective evaluation of cardiac risk indices for patients undergoing noncardiac surgery.  Ann Intern Med.2000;133:356-359.
Khuri SF, Daley J, Henderson W.  et al.  The National Veterans Administration Surgical Risk Study: risk adjustment for the comparative assessment of the quality of surgical care.  J Am Coll Surg.1995;180:519-531.
Lee TH, Marcantonio ER, Mangione CM.  et al.  Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery.  Circulation.1999;100:1043-1049.
Lawrence VA, Hilsenbeck SG, Mulrow CD, Dhanda R, Sapp J, Page CP. Incidence and hospital stay for cardiac and pulmonary complications after abdominal surgery.  J Gen Intern Med.1995;10:671-678.
Goldman L. Multifactorial index of cardiac risk in noncardiac surgery: ten-year status report.  J Cardiothorac Anesth.1987;1:237-244.
Lee TH. Reducing cardiac risk in noncardiac surgery.  N Engl J Med.1999;341:1838-1840.
Collins TC, Daley J, Henderson WH, Khuri SF. Risk factors for prolonged length of stay after major elective surgery.  Ann Surg.1999;230:251-259.
Belzberg H, Rivkind AI. Preoperative cardiac preparation.  Chest.1999;115(5 suppl):82S-95S.
Merli GJ, Weitz HH. The medical consultant.  Med Clin North Am.1987;71:353-355.
Merli GJ, Weitz HH. Approaching the surgical patient: role of the medical consultant.  Clin Chest Med.1993;14:205-210.
Eagle KA, Berger PB, Calkins H.  et al.  ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [American College of Cardiology Web site]. Available at: http://www.acc.org/clinical/guidelines/perio/update/pdf/perio_update.pdf. Accessibility verified February 19, 2002.
American College of Physicians.  Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery.  Ann Intern Med.1997;127:309-312.
Detsky AS, Abrams HB, Forbath N, Scott JG, Hilliard JR. Cardiac assessment for patients undergoing noncardiac surgery: a multifactorial clinical risk index.  Arch Intern Med.1986;146:2131-2134.
L'Italien GJ, Paul SD, Hendel RC.  et al.  Development and validation of a Bayesian model for perioperative cardiac risk assessment in a cohort of 1081 vascular surgical candidates.  J Am Coll Cardiol.1996;27:779-786.
Steyerberg EW, Kievit J, de Mol Van Otterloo JC, van Bockel JH, Eijkemans MJ, Habbema JD. Perioperative mortality of elective abdominal aortic aneurysm surgery: a clinical prediction rule based on literature and individual patient data.  Arch Intern Med.1995;155:1998-2004.
Miller K, Atzenhofer K, Gerber G, Reichel M. Risk prediction in operatively treated fractures of the hip.  Clin Orthop.1993;293:148-152.
Jivegard L, Bergqvist D, Holm J.  et al.  Preoperative assessment of the risk for cardiac death following thrombo-embolectomy for acute lower limb ischaemia.  Eur J Vasc Surg.1992;6:83-88.
Larsen SF, Olesen KH, Jacobsen E.  et al.  Prediction of cardiac risk in non-cardiac surgery.  Eur Heart J.1987;8:179-185.
Eagle KA, Rihal CS, Mickel MC, Holmes DR, Foster ED, Gersh BJ.and the CASS Investigators and University of Michigan Heart Care Program.  Cardiac risk of noncardiac surgery: influence of coronary disease and type of surgery in 3368 operations: Coronary Artery Surgery Study.  Circulation.1997;96:1882-1887.
Foster ED, Davis KB, Carpenter JA, Abele S, Fray D. Risk of noncardiac operation in patients with defined coronary disease: the Coronary Artery Surgery Study (CASS) registry experience.  Ann Thorac Surg.1986;41:42-50.
Hassan SA, Hlatky MA, Boothroyd DB.  et al.  Outcomes of noncardiac surgery after coronary bypass surgery or coronary angioplasty in the Bypass Angioplasty Revascularization Investigation (BARI).  Am J Med.2001;110:260-266.
Reich DL, Bodian CA, Krol M, Kuroda M, Osinski T, Thys DM. Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery.  Anesth Analg.1999;89:814-822.
Hewer I, Drew B, Karp K, Stotts N. The utilization of automated ST segment analysis in the determination of myocardial ischemia.  AANA J.1997;65:351-356.
Wallace A, Layug B, Tateo I.  et al.  Prophylactic atenolol reduces postoperative myocardial ischemia: McSPI Research Group.  Anesthesiology.1998;88:7-17.
Raby KE, Barry J, Creager MA, Cook EF, Weisberg MC, Goldman L. Detection and significance of intraoperative and postoperative myocardial ischemia in peripheral vascular surgery.  JAMA.1992;268:222-227.
Mangano DT, Hollenberg M, Fegert G.  et al. and the Study of Perioperative Ischemia (SPI) Research Group.  Perioperative myocardial ischemia in patients undergoing noncardiac surgery, I: incidence and severity during the 4 day perioperative period.  J Am Coll Cardiol.1991;17:843-850.
Landesberg G, Luria MH, Cotev S.  et al.  Importance of long-duration postoperative ST-segment depression in cardiac morbidity after vascular surgery.  Lancet.1993;341:715-719.
Godet G, Coriat P, Baron JF.  et al.  Prevention of intraoperative myocardial ischemia during noncardiac surgery with intravenous diltiazem: a randomized trial versus placebo.  Anesthesiology.1987;66:241-245.
Antunes E, Serra J, Ferreira R.  et al.  Effects of diltiazem on myocardial ischemia in patients with coronary artery disease.  Rev Port Cardiol.1993;12:219-223.
Coriat P. Intravenous nitroglycerin dosage to prevent intraoperative myocardial ischemia during noncardiac surgery.  Anesthesiology.1986;64:409-410.
Dodds TM, Stone JG, Coromilas J, Weinberger M, Levy DG. Prophylactic nitroglycerin infusion during noncardiac surgery does not reduce perioperative ischemia.  Anesth Analg.1993;76:705-713.
Smulyan H, Weinberg SE, Howanitz PJ. Continuous propranolol infusion following abdominal surgery.  JAMA.1982;247:2539-2542.
Pasternack PF, Grossi EA, Baumann FG.  et al.  Beta blockade to decrease silent myocardial ischemia during peripheral vascular surgery.  Am J Surg.1989;158:113-116.
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;88:477-482.
Shojania KG, Duncan BW, McDonald KM, Wachter RM. Making Health Care Safer: A Critical Analysis of Patient Safety Practices: Evidence Report/Technology Assessment No. 43. Rockville, Md: Agency for Healthcare Research and Quality; 2001. Publication 01-E058.
Mangano DT, Goldman L. Preoperative assessment of patients with known or suspected coronary disease.  N Engl J Med.1995;333:1750-1756.
Juni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials.  BMJ.2001;323:42-46.
Juni P, Witschi A, Bloch R, Egger M. The hazards of scoring the quality of clinical trials for meta-analysis.  JAMA.1999;282:1054-1060.
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;13:555-561.
Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery: Multicenter Study of Perioperative Ischemia Research Group.  N Engl J Med.1996;335:1713-1720.
Stone JG, Foex P, Sear JW, Johnson LL, Khambatta HJ, Triner L. Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent.  Anesthesiology.1988;68:495-500.
Urban MK, Markowitz SM, Gordon MA, Urquhart BL, Kligfield P. Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia.  Anesth Analg.2000;90:1257-1261.
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;341:1789-1794.
Mangano DT. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.  N Engl J Med.1997;336:1452.
Reis SE, Feldman AH. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.  N Engl J Med.1997;336:1453.
Petros JA. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.  N Engl J Med.1997;336:1452.
Litwack RS, Gilligan DM, DeGruttola V. Beta-blockade for patients undergoing vascular surgery.  N Engl J Med.2000;342:1052.
Feldman T, Fusman B, Mckinsey JF. Beta-blockade for patients undergoing vascular surgery.  N Engl J Med.2000;342:1051-1052.
Poldermans D, Boersma E. Beta-blockade for patients undergoing vascular surgery.  N Engl J Med.2000;342:1052-1053.
Hammon Jr JW, Wood AJ, Prager RL, Wood M, Muirhead J, Bender Jr HW. Perioperative beta blockade with propranolol: reduction in myocardial oxygen demands and incidence of atrial and ventricular arrhythmias.  Ann Thorac Surg.1984;38:363-367.
Lamb RK, Prabhakar G, Thorpe JA, Smith S, Norton R, Dyde JA. The use of atenolol in the prevention of supraventricular arrhythmias following coronary artery surgery.  Eur Heart J.1988;9:32-36.
Bayliff CD, Massel DR, Inculet RI.  et al.  Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery.  Ann Thorac Surg.1999;67:182-186.
Shammash JB, Trost JC, Gold JM, Berlin JA, Golden MA, Kimmel SE. Perioperative beta-blocker withdrawal and mortality in vascular surgical patients.  Am Heart J.2001;141:148-153.
Goldman L. Noncardiac surgery in patients receiving propranolol: case reports and recommended approach.  Arch Intern Med.1981;141:193-196.
Gilligan DM, Chan WL, Stewart R, Oakley CM. Adrenergic hypersensitivity after beta-blocker withdrawal in hypertrophic cardiomyopathy.  Am J Cardiol.1991;68:766-772.
Swedberg K, Hjalmarson A, Waagstein F, Wallentin I. Adverse effects of beta-blockade withdrawal in patients with congestive cardiomyopathy.  Br Heart J.1980;44:134-142.
Miller RR, Olson HG, Amsterdam EA, Mason DT. Propranolol-withdrawal rebound phenomenon: exacerbation of coronary events after abrupt cessation of antianginal therapy.  N Engl J Med.1975;293:416-418.
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;285:1865-1873.
Goldman L. Assessing and reducing cardiac risks of noncardiac surgery.  Am J Med.2001;110:320-323.
Zaugg M, Tagliente T, Lucchinetti E.  et al.  Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery.  Anesthesiology.1999;91:1674-1686.
Fallowfield JM, Marlow HF. Propranolol is contraindicated in asthma.  BMJ.1996;313:1486.
van Zyl AI, Jennings AA, Bateman ED, Opie LH. Comparison of respiratory effects of two cardioselective beta-blockers, celiprolol and atenolol, in asthmatics with mild to moderate hypertension.  Chest.1989;95:209-213.
Ellis JE, Drijvers G, Pedlow S.  et al.  Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.  Anesth Analg.1994;79:1133-1140.
Quintin L, Bouilloc X, Butin E.  et al.  Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study.  Anesth Analg.1996;83:687-695.
Stuhmeier KD, Mainzer B, Cierpka J, Sandmann W, Tarnow J. Small, oral dose of clonidine reduces the incidence of intraoperative myocardial ischemia in patients having vascular surgery.  Anesthesiology.1996;85:706-712.
Fox K, Dargie HJ, de Bono DP, Oliver MF, Wulfert E, Kharkevitch T. Effect of an alpha(2) agonist (mivazerol) on limiting myocardial ischaemia in stable angina.  Heart.1999;82:383-385.
Oliver MF, Goldman L, Julian DG, Holme I. Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease: the European Mivazerol Trial (EMIT).  Anesthesiology.1999;91:951-961.
Poldermans D, Boersma E, Bax JJ.  et al.  Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery.  Eur Heart J.2001;22:1353-1358.
Krumholz HM, Radford MJ, Wang Y, Chen J, Marciniak TA. Early beta-blocker therapy for acute myocardial infarction in elderly patients.  Ann Intern Med.1999;131:648-654.
Krumholz HM, Radford MJ, Wang Y, Chen J, Heiat A, Marciniak TA. National use and effectiveness of beta-blockers for the treatment of elderly patients after acute myocardial infarction: National Cooperative Cardiovascular Project.  JAMA.1998;280:623-629.
White CM. Prevention of suboptimal beta-blocker treatment in patients with myocardial infarction.  Ann Pharmacother.1999;33:1063-1072.
Wang TJ, Stafford RS. National patterns and predictors of beta-blocker use in patients with coronary artery disease.  Arch Intern Med.1998;158:1901-1906.
Soumerai SB, McLaughlin TJ, Spiegelman D, Hertzmark E, Thibault G, Goldman L. Adverse outcomes of underuse of beta-blockers in elderly survivors of acute myocardial infarction.  JAMA.1997;277:115-121.
Radford MJ, Krumholz HM. Beta-blockers after myocardial infarction—for few patients, or many?  N Engl J Med.1998;339:551-553.
Gurwitz JH, Goldberg RJ, Chen Z, Gore JM, Alpert JS. Beta-blocker therapy in acute myocardial infarction: evidence for underutilization in the elderly.  Am J Med.1992;93:605-610.
Packer M. Current role of beta-adrenergic blockers in the management of chronic heart failure.  Am J Med.2001;110:81S-94S.
Heart Failure Society of America.  HFSA guidelines for management of patients with heart failure caused by left ventricular systolic dysfunction: pharmacological approaches.  Pharmacotherapy.2000;20:495-522.
Fleisher LA, Eagle KA. Lowering cardiac risk in noncardiac surgery.  N Engl J Med.2001;345:1677-1682.

Letters

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 203

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles