The American Journal of Medicine
Volume 122, Issue 3 , Pages 222-229, March 2009

Perioperative Beta-blockers for Major Noncardiac Surgery: Primum Non Nocere

  • Vineet Chopra, MD

      Affiliations

    • Division of General Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor
    • Corresponding Author InformationRequests for reprints should be addressed to Vineet Chopra, MD, University of Michigan Health System, 3119 Taubman Center, 1500 E, Medical Ctr Dr., SPC 5376, Ann Arbor, MI 48109
    • ,
  • Benjamin Plaisance, MD

      Affiliations

    • Division of General Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor
    • ,
  • Erdal Cavusoglu, MD

      Affiliations

    • Division of Cardiology, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn
    • ,
  • Scott A. Flanders, MD

      Affiliations

    • Division of General Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor
    • ,
  • Kim A. Eagle, MD

      Affiliations

    • Division of Cardiovascular Medicine, Department of Medicine, University of Michigan Health System, Ann Arbor

published online 29 January 2009.

Article Outline

Abstract 

Recent studies have called into question the benefit of perioperative beta blockade, especially in patients at low to moderate risk of cardiac events. Once considered standard of care, the role of beta-blocker therapy now lies mired in conflicting data that are difficult to apply to the at-risk patient. We provide an overview of the evolution of perioperative beta blockade, beginning with the physiology of the adrenergic system, with emphasis on the biologic rationale for the perioperative implementation of beta-blockers. Although initial studies were small in size and statistically limited, early data showed cardiac benefit with the use of perioperative beta-blockers. However, larger, more recent studies now suggest a lack of benefit and potential harm from this practice. This paradigm holds true especially in those at low-to-moderate cardiovascular risk profiles. Potential explanations for these paradoxical results are discussed, stressing the key differences between earlier and current studies that may explain these divergent outcomes. We conclude by commenting on performance measures as they relate to perioperative beta-blockers and make recommendations for the continued safe implementation of this practice.

Keywords: Beta-blockers, Noncardiac surgery, Perioperative risk reduction, POISE

 

The story of beta-blockers as risk-reducing agents in perioperative medicine is a tale of progressive scientific inquiry. For instance, it was once theorized that blockade of the beta-receptor suppressed protective mechanisms geared to prevent cardiovascular collapse during periods of surgical stress. This theory was so widely accepted that the routine discontinuation of beta-blockers before elective cardiac surgery was embraced by the scientific community in the 1970s.1 The hypothesis that beta-blockers actually improve cardiovascular outcomes during surgery was tested in a 1973 trial, the results of which showed a decrease in myocardial ischemia, ventricular arrhythmia, and blunting of the hypertensive response on intubation associated with this therapy.2

Clinical Significance

 


•A biological rationale for benefit from perioperative beta-blockers exists.

•Initial trials supporting perioperative beta blockade suffered small construct and limited design, and thus cannot determine current practice.

•Recent studies suggest caution with beta blockade, especially in low/moderate cardiovascular risk profiles.

•Differences in trial design and drug regimen explain divergent study outcomes.

•Authorities may have perpetuated broader implementation of perioperative beta blockade than was supported by the available science.

As clinical data accumulated, beta-blockers quickly became first-line therapy in acute myocardial infarction, stable coronary artery disease, and systolic heart failure.3, 4, 5 Their use also grew in the perioperative treatment of patients undergoing vascular surgery with coronary ischemia,6 ultimately leading to a Class I recommendation (evidence that a given procedure is useful and effective) in the 2002 American Heart Association/American College of Cardiology Joint Guidelines.7 A Class IIa recommendation (conflicting evidence in favor of usefulness) was provided for patients with either untreated hypertension, coronary artery disease, or the presence of risk factors for coronary artery disease. The medical community thus began to enthusiastically implement these agents, extending their use to populations not shown to derive benefit; namely, patients at low/moderate cardiovascular risk and those undergoing nonvascular surgery.8

A number of seminal trials published over the past decade have demonstrated a lack of benefit in the perioperative application of beta blockade. In fact, a recent large randomized study showed potential for harm in the form of increased rates of stroke and overall mortality.9 In addition, several trials have reported intraoperative complications in patients on beta-blocker therapy.10, 11 Thus, mounting evidence has called into question ubiquitous perioperative beta blockade. The clinical dilemma faced by today's practitioner consequently lies in identifying which patients might benefit and which might be harmed by this intervention.

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Physiology and Pharmacology of Beta-Adrenergic Receptors and their Blockers 

Beta-adrenergic blockers are a class of medications targeted at the blockade of postsynaptic beta-adrenergic receptors. These receptors are cell surface-specific and are found throughout various tissues. Several sub-types of beta receptors exist, including beta-1 (found in the myocardium, kidney, eye), beta-2 (adipose tissue, pancreas, liver, smooth and skeletal muscle), and beta-3 (involved with metabolic regulation and lipolytic pathways). On a molecular level, they are linked to G-coupled proteins activating adenylyl cyclase, initiating intracellular events via cyclic adenosine monophosphate. Interruption of this pathway prevents activation of excitatory channels, leading to the benefits associated with this class of drugs.

Beta-blockers differ considerably in their pharmacokinetic and pharmacodynamic profiles. For example, bisoprolol and atenolol are long acting (t/2 10-11 hours vs 6 hours, respectively), whereas metoprolol is relatively short acting (t/2 3.5 hours). A longer-acting preparation of metoprolol (t/2 of 24 hours) is available and was used in the POISE study.9 Beta-blockers also differ in their affinity for target receptors, mediating selective clinical and hemodynamic effects through variable receptor agonism.

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Perioperative Beta-Adrenergic Blockade: An Ideal Target 

Following surgery, a number of protective physiologic responses are activated (Figure). For example, a significant catecholamine surge occurs after surgery, producing important sympathetic effects, including measurable elevations in heart rate and blood pressure.12 In the perioperative setting, such responses are potentially deleterious and can precipitate cardiovascular events.13 Experimental perioperative models demonstrate heightened vasomotor reactivity, rupture of vulnerable coronary plaques, and thrombus formation, ultimately leading to vessel occlusion and cardiac events. These “culprit” lesions are difficult to detect, rendering preoperative intervention difficult and subjective.14 Finally, increases in circulating coagulation factors, reduced fibrinolytic activity, and heightened systemic inflammatory responses interplay to produce a hazardous perioperative milieu.15

It is thus not surprising that cardiovascular complications after noncardiac surgery range from 2.5 to 10 in every 100 patients.16 In the specific subgroup of patients with known coronary artery disease, the most important predictors of morbidity remain perioperative ischemia and nonfatal myocardial infarction. Postoperative ischemia has been shown to account for a 9-fold increase in the odds of cardiovascular death, myocardial infarction, or unstable angina, and thus forms an important target for remediation in the preoperative setting.17

Numerous properties of beta-blockers make them ideal therapy in this situation. Beta-blockers limit and attenuate both sympathetic and neuroendocrine responses to stress during surgery.18 In individuals with preexisting cardiovascular disease, beta-blockers reduce perioperative ischemia by balancing myocardial oxygen supply and demand mismatch.19 They prevent ventricular arrhythmias and attenuate perioperative inflammatory markers and free radicals, variables associated with precipitation of acute coronary syndromes.20 On a cellular level, beta-blockers suppress intracellular lipolysis, reducing myocardial oxygen consumption via promotion of glucose metabolism over fatty acids.21 They increase the stability of atherosclerotic plaque and suppress catecholamine production during the first 48 hours after surgery.22 Thus, due to their multifaceted effects, beta-blockers mitigate cardiovascular stress from surgery.

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Initial Clinical Studies Supporting Perioperative Beta Blockade 

As a plausible physiologic mechanism of benefit exists for perioperative beta-blockers, initial clinical studies sought to demonstrate this fact. Among the first of these studies was published by Stone et al in 1988.23 These investigators conducted a trial with hypertensive patients monitored via Holter for ischemia during anesthesia and surgery. The study randomized 128 patients to treatment with a single oral preoperative dose of labetalol, atenolol, or oxprenolol. The study reported myocardial ischemia in 11 of 39 control subjects versus 2 of 89 study patients (28% vs 2%, P <.001). Although small and unblinded, the authors concluded that a single dose of preoperative beta-blocker prevented ischemia by limiting heart rate accelerations in hypertensive patients.

In 1996, Mangano et al24 performed the first randomized controlled trial on perioperative beta blockade, comparing atenolol to placebo in 200 patients with known coronary artery disease undergoing noncardiac surgery. Analyses at study completion showed that overall mortality was 55% lower in the atenolol group than the placebo group. Although no difference in immediate perioperative cardiac events was observed, the benefit of beta blockade was evident at 6-month follow-up, where the rate of cardiac events was 0 in the study group versus 12 in the placebo group (P <.001). Further, the time to first event was 6 days for placebo (vs 158 days for atenolol), indicating an acute increase in events in those untreated with beta-blockers. Like Stone et al,23 the authors noted that controlling heart rate prevented postoperative ischemia. The trial has been criticized, however, due to significant discrepancies in the 2 study groups and exclusion of deaths in the immediate postoperative period, which (if included at endpoint analyses), would have negated the outcome of the study.25 Nonetheless, the article remains frequently cited as it offered a novel, inexpensive means of preventing perioperative cardiac death.

Poldermans et al26 followed the Mangano study with the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo (DECREASE) trial, which involved 112 high-risk patients (clinical markers of risk and inducible myocardial ischemia on dobutamine echocardiography) randomized to either bisoprolol or placebo before major vascular surgery. Importantly, the study protocol called for the initiation of bisoprolol at least 1 week before surgery (mean=37 days) with titration of the drug to achieve a heart rate of 60/min. The study was stopped prematurely when interim analyses revealed a 10-fold reduction in the incidence of perioperative cardiac death and myocardial infarction versus placebo (3.4% vs 34%; P <.001). The study thus reaffirmed the value of perioperative beta-blockers in a high-risk cohort.

A systematic review published by Auerbach and Goldman unified the findings of these initial studies.27 When examining myocardial ischemia, the authors found “modest” numbers needed to treat of 2.5-6.7, with the greatest benefit evident in high-risk patients. The review concluded that the benefits of beta blockade were “without known adverse effect.”

It is pertinent to note that many of these initial studies were small in size and insufficiently powered to address effects on cardiovascular outcomes. In addition, some of these studies used surrogate endpoints (eg, electrocardiogram ischemia) to show benefit. Thus, limitation in study design and the potential for bias might have led to error in the interpretation and implementation of data from these trials (Table 1).

Table 1. Size, Design, Endpoints and Limitations of Early Perioperative β-Blocker Trials
Study/Reference(n)Study DesignPrimary EndpointLimiting Factors Identified
Stone et al23128Preoperative single dose of oral labetolol, atenolol, olprenolol vs placeboIncidence of Holter Documented Ischemia
Small study cohort

Unblinded design

Type(s) of surgery unidentified

No baseline demographic data reported

Mangano et al24200Oral atenolol 0, 50, or 100 mg at time of anesthesia vs placeboAll-cause mortality, cardiac death and postoperative ischemia
Less CAD in beta-blocker group

More ACE-I usage in beta-blocker group

Placebo arm ↑ patients with DM and prior MI

Excluded deaths in the immediate postoperative period which would have changed study findings at 2 years

Wallace et al18200Oral atenolol 0, 50, or 100 mg vs placeboIncidence of myocardial ischemia during the first week of surgery
↑ Pre-existing HTN in beta-blocker group

Control had beta-blocker withdrawn if already on this Rx, possibly precipitating withdrawal and changing outcomes

Poldermans et al26112Oral bisoprolol (titrated to heart rate) before surgery (≈37 days) vs placebo
Cardiac death

Nonfatal MI


Unblinded study

Patients already on beta-blockers were excluded

8 patients with extensive ischemia were excluded

Zaugg et al4163Intra and post-op atenolol 10-20 mg vs standard careMeasurement of catecholamine stress response hormonesArgues against blunting of stress-catecholamine surge as a protective mechanism of beta blockade
Urban et al42107IV esmolol on day of surgery followed by 25 mg BID metoprolol vs placebo
Incidence of ST segment changes

Incidence of adverse cardiac outcomes (death, MI)


Unexpected low rate of post operative MI in placebo

Did not prove beta-blockers↓cardiac morbidity

1/3 of placebo group concomitantly received beta-blockers

Boersma et al431351Follow-up study to Poldermans—oral bisoprolol vs standard careCardiac death and nonfatal MI within 30 days of surgery
Retrospective study-design

Unblinded

Low observed event rates vs expected

Brady et al28103Oral metoprolol 50 mg BID preoperatively+7 day postop.Cardiac death and nonfatal MI within 30 days of surgery and LOS
High rate of CV events (33%) uncharacteristic

Randomization arms uneven

Abbreviations: CAD=coronary artery disease; ACE-I=angiotensin-converting enzyme inhibitor; DM=diabetes mellitus; MI=myocardial infarction; HTN=hypertension; BID=twice a day; CV=cardiovascular; LOS=length of stay.

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Origins of Concern: More Recent Studies 

Recent clinical trials have reported adverse effects from the use of perioperative beta-blockers, particularly in patients at low to moderate risk of cardiac events. These studies have raised concern in the broad endorsement of this practice.

The 2006 Metoprolol after Vascular Surgery (MaVS) study sought to answer whether perioperative administration of metoprolol was associated with a reduction in cardiac events in patients undergoing vascular surgery.10 The trial randomized 496 patients without known ischemic heart disease in a double-blinded manner to placebo (n=250) or perioperative metoprolol (n=246) dosed according to patient body weight (≥75 kg: 100 mg; 40-75 kg: 50 mg; ≤40 kg: 25 mg). Metoprolol was given 2 hours preoperatively and was continued for 5 days or until hospital discharge. Mean follow-up was 6 months, with analysis for the composite endpoint of cardiac death, nonfatal myocardial infarction, unstable angina, congestive heart failure, or arrhythmia requiring treatment, performed at 30 days. The study reported that while the postoperative heart rate was lower in the metoprolol group (69.4 vs 79.1 beats per minute, P <.001), the rate of intraoperative complications, including hypotension requiring treatment (46.3% vs 33.6%, P <.001) and bradycardia requiring treatment (21.5% vs 7.6%, P <.001), was significantly higher. This mirrored the results of prior studies,11, 28 casting a shadow on the risk:benefit profile of beta-blockers. Importantly, MaVS showed no difference in cardiac events in patients receiving perioperative beta-blockers versus those receiving placebo (10.2% vs 12%, P=.57), thus demonstrating no benefit, but potential harm from this practice.

The findings of MaVS were similar to those of 2 other studies: Diabetic Post Operative Mortality and Morbidity (DIPOM) and the Perioperative Beta-Blockade studies (POBBLE).11, 28 Comparable in construct to MaVS, DIPOM assessed the benefit of metoprolol in 921 diabetic patients without coronary artery disease undergoing vascular surgery. Results showed that perioperative metoprolol failed to reduce cardiac events but did cause intraoperative hypotension and bradycardia. Similarly, POBBLE randomized 103 patients undergoing vascular surgery to 50 mg metoprolol twice a day or placebo, starting <24 hours before surgery and continued 7 days after. Results from POBBLE also did not show benefit in cardiovascular outcomes, with events occurring in 32% vs. 34% in the metoprolol and placebo arms, respectively. MaVS, DIPOM, and POBBLE thus suggested caution in the use of beta-blockers in patients without defined preoperative ischemia.

In a landmark review, Lindenauer et al29 performed a retrospective cohort study analyzing the effects of beta-blockers according to preexisting cardiac risk defined by Lee's Revised Cardiac Risk Index (Table 2). This approach was unique in that it attempted to identify risk categories that may benefit or be harmed by beta-blockers. The study reviewed 782,969 patients, of whom 122,338 (16%) received beta blockade during the first 2 days of hospitalization. Within this study cohort, 14% had a Revised Cardiac Risk Index score of 0, portending low cardiovascular risk, whereas 44% had a score of 4 or higher, suggestive of high risk. Analysis of results revealed that the relationship between perioperative beta blockade and the risk of death varied directly with cardiac risk; thus, individuals at high risk showed the greatest benefit from beta blockade, whereas those in the low to moderate risk categories showed a trend toward harm from this practice owing to bradycardia and hypotension.29

Table 2. Lee's Revised Cardiac Risk Index (RCRI)
Clinical ParameterRCRI Point
Prior TIA or CVA1
Diabetes mellitus requiring insulin therapy1
Serum creatinine ≥2 mg/dL1
History of coronary artery disease1
High-risk surgery (chest, abdominal or suprainguinal vascular surgery)1

Abbreviations: TIA=transient ischemic attack; CVA=cardiovascular accident.

Low risk=0-1; moderate risk=2; high risk ≥3. Event rates increase as RCRI score increases.

The Perioperative Ischemic Evaluation (POISE) study published in 2008 remains the largest randomized controlled trial examining the role of beta-blockers in the perioperative setting.9 The study prospectively randomized 8351 patients with or at risk for coronary artery disease scheduled to undergo noncardiac surgery into 2 arms receiving either oral extended-release metoprolol succinate (n=4174) or placebo (n=4177). The trial protocol called for administration of 100 mg of the study drug 2-4 hours before surgery, with a second dose 6 hours after surgery if prespecified hemodynamic parameters remained acceptable. Patients were then given 200 mg extended-release metoprolol 12 hours after their postoperative dose, with this regimen continued for 30 days.

Results from POISE showed cardiac benefit. Fewer patients in the metoprolol group reached the primary endpoint of death, nonfatal myocardial infarction, or nonfatal cardiac arrest (244 [5.8%] vs 290 [6.9%]) than in the placebo group (hazard ratio 0.84, 95% confidence interval, 0.70-0.99, P=.0399). Additionally, fewer patients in the metoprolol-treated group had a myocardial infarction (176 [4.2%] vs 239 [5.7%], hazard ratio 0.73, 95% confidence interval, 0.60-0.89, P=.0017). However, there were more deaths in the metoprolol group (129 vs 97) than placebo. Subgroup analyses indicated that the major contributor to mortality in the beta-blocker group were noncardiac deaths. In addition, significantly more patients in the metoprolol group developed ischemic stroke (41 vs 19) compared with placebo. Predictably, clinically significant hypotension and bradycardia was noted in the metoprolol group (15% and 6.6%, respectively). POISE thus demonstrated that there is significant risk in the assumption that a perioperative beta-blocker regimen has benefit without harm, illustrating that for every 1200 patients treated, metoprolol would prevent 15 myocardial infarctions at a cost of 8 excess deaths and 5 disabling strokes.

In a recent meta-analysis, Devereaux et al30 reviewed 22 trials randomizing 2437 patients and reported that perioperative beta-blockers were not associated with statistically significant benefits on either individual or composite cardiovascular outcomes. Importantly, this article did confirm an increased risk of bradycardia and hypotension, and showed that the evidence for perioperative beta blockade was “insufficient and inconclusive,” especially in those at low to moderate risk of adverse cardiovascular outcomes.

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Deciphering Divergent Study Results: Explanations for Conflicting Data 

Several aspects help explain the conflicting evidence for perioperative beta-blocker use (Table 3). First, the preoperative timing of beta blockade may have influenced study outcomes. For example, the Mangano protocol24 called for beta-blockers at induction of anesthesia, while Poldermans et al26 initiated bisoprolol at an average of 37 days before surgery. The importance of time of initiation lies in the fact that acute effects of beta blockade (decreased heart rate, systolic pressure, and reduced myocardial ischemia) may not fully explain the benefit of perioperative therapy, as anti-inflammatory and plaque-stabilizing properties take days to develop.22

Table 3. Studies Grouped According to Outcomes associated with Perioperative β-Blockers
Studies Showing Benefit with Perioperative β-BlockadeStudies Showing Harm with Perioperative β-Blockade
YearInvestigatorsDesignSize (n)YearInvestigatorsDesignSize (n)Nature of Harm
1988Stone et al23R NB PCT1281988Stone et al23R NB PCT128Bradycardia requiring Rx
1996Mangano et al24R DB PCT2002005Devereaux et al30RV MA2437Bradycardia requiring Rx
1999Raby et al44R DB PCT262005Lindenauer et al29RP PCT A119,632Bradycardia and HypoTN
1999Poldermans et al26R NB PCT1122005DIPOM11R DB PCT921↑ Intra-operative HypoTN
2000Urban et al42R NB PCT1072008MaVS10R DB PCT496↑ Intra-operative HypoTN
2001Boersma et al43RP13512008POISE9R DB PCT8351↑ Death and ↑ Stroke

Abbreviations: A=analyses; R=randomized; RP=retrospective; RV=review; NB=nonblinded; DB=double blinded; MA=meta-analyses; PCT=placebo controlled trial; Rx=treatment.

Secondly, the type of beta-blocker used may have led to different study outcomes. The perioperative benefit from beta blockade is thought to arise primarily via the negative ino- and chronotropic effects through beta-1 blockade. Dual beta-1 and beta-2 receptor inhibition is unwelcome in the hyperadrenergic perioperative environment, as it would lead to unopposed alpha stimulation. This may explain why bisoprolol (highly beta-1 selective) has been associated with better results, whereas metoprolol and atenolol (moderately beta-1 selective) are associated with mixed results in clinical trials. Other drug properties such as degree of absorption, volume of distribution, plasma protein binding, and drug half-life might also contribute to study outcomes, as longer-acting agents show greater cardioprotection than short-acting agents.31

An important parameter in perioperative beta-blocker studies remains the balance between dose adjustments of drug to achieve target heart rates in relation to drug side effects. This is graphically illustrated in POISE, where the increased rate of ischemic stroke in combination with intraoperative bradycardia and hypotension suggest an over-treatment effect.32 Conversely, recent studies33, 34 and a large meta-analysis35 have confirmed that heart rate control with beta-blockers avoiding hypotension is associated with improved cardiovascular outcomes.

Finally, estimating baseline cardiac risk remains an important parameter in determining benefit of beta blockade. As confirmed by Lindenauer et al,29 the data have shown that beta-blockers do benefit patients with high cardiovascular risk, while harm may occur to low-risk patients. This paradigm may explain the adverse findings of MAVS, DIPOM, and POBBLE, as these patients were among the low to moderate risk category. The 2007 American College of Cardiology/American Heart Association Update on Perioperative Risk Reduction highlight this fact, restricting their Class I indication to those already on beta-blockers and to those with known ischemia undergoing high-risk surgery.

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Perioperative Beta-Blockers: Not Quite Ready for a Quality Revolution 

Based on the positive results of preliminary studies, numerous regulatory agencies were quick to endorse perioperative beta blockade. The Leapfrog Group for Patient Safety, for example, promoted perioperative beta blockade as a patient safety measure in their annual report. Subsequently, the National Quality Forum, Surgical Care Improvement Project, and the Agency for Healthcare Research and Quality also issued statements of support for this measure, identifying the perioperative implementation of beta-blockers as a “clear opportunity for safety improvement in surgical outcomes.”36, 37

It is well known that performance measures can serve as a catalyst for implementing quality improvement efforts.38 Thus, health care institutions have faced increased pressure in not only reporting, but also implementing perioperative beta blockade. As has been argued with the rapid implementation of other performance metrics,39 regulatory agencies may have inadvertently helped perpetuate a far wider implementation of perioperative beta blockade than was supported by the available science. We are thus reminded that performance metrics must be based on both the highest level of clinical evidence and affirmative effect on patient outcomes. Such was not the case with perioperative beta blockade. Importantly, several agencies have revised their stance on this issue.40

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Conclusion 

Cumulative data over the past decade have shown that there is danger in extending the original narrow indication of perioperative beta blockade. We summarize vital clinical recommendations for the ongoing use of perioperative beta blockade in Table 4. The literature has summarily revealed that attention to both patient risk and beta-blocker profile is critical to the safe and effective implementation of this therapy. Although there remains an overwhelming need for further study in this area, our best approach is captured by the truism Primum Non Nocere. First, do no harm.

Table 4. Clinical Recommendations for Implementing β-blockers in the Perioperative Setting
RecommendationDescription and Rationale
Monitor perioperative heart rate and blood pressure
Serially assess hemodynamic measures at prespecified intervals

Withhold or administer beta-blocker according to preset thresholds/criteria

Such an approach may help detection of issues such as hypovolemia, infection, sepsis

Implement a “run-in” phase for perioperative beta blockade
Initiate therapy at least 7 days before operative intervention

Allows for both acute (hemodynamic) and delayed (anti-inflammatory) effects of beta-blockers

Promotes early recognition of adverse effects (eg, bradycardia, hypotension, bronchospasm)

Adjust dose to achieve a target heart-rate of 60 beats per minute, avoiding hypotension
Heart rate control remains the major mechanism of beta-blocker benefit

Helps identify and prevent perioperative bradycardia and intraoperative hypotension

Can require variable doses of drug and thus allows for individualization of therapy

Recognize that beta-blockers differ considerably
Short vs long-acting agents, varying clinical effects based on receptor agonism

IV vs PO route of administration important as IV route can rapidly precipitate side effects

Tailor therapy to maintain same agent/dose(s) as in the preoperative setting

Continue beta-blockers if already on this therapy
Sudden withdrawal of beta-blockers known to cause upregulated beta-receptor state

Class I ACC/AHA recommendation, especially if an original indication already exists

Strive to maintain same agent as the preoperative setting

Abbreviations: IV=intravenous; PO=by mouth; ACC/AHA=American College of Cardiology/American Heart Association.

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 Funding: None; no funding received.

 Conflicts of Interest: There are no conflicts of interest for any of the authors.

 Authorship: All authors had access to the data and a role in writing the manuscript.

PII: S0002-9343(08)01121-2

doi:10.1016/j.amjmed.2008.11.004

The American Journal of Medicine
Volume 122, Issue 3 , Pages 222-229, March 2009

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