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Anesth Analg 2007;104:27-41
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000247805.00342.21

CARDIOVASCULAR ANESTHESIA

Perioperative ß-Blockers for Preventing Surgery-Related Mortality and Morbidity: A Systematic Review and Meta-Analysis

Franz Wiesbauer, MD, MPH, Oliver Schlager, MD, Hans Domanovits, MD, Brigitte Wildner, MSc, Gerald Maurer, MD, Marcus Muellner, MD, MSc, Hermann Blessberger, and Martin Schillinger, MD

From the Departments of *Cardiology, {dagger}Emergency Medicine, {ddagger}Angiology, and §University Library, Vienna General Hospital, Medical University, Vienna, Austria.

Address correspondence and reprint requests to Franz Wiesbauer, MD, MPH, Department of Internal Medicine II, Cardiology Unit, Vienna General Hospital, Medical University, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Address e-mail to franz.wiesbauer{at}meduniwien.ac.at.


   Abstract
Top
 Abstract
Introduction
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
BACKGROUND: Perioperative ß-blockers are suggested to reduce cardiovascular mortality, myocardial–ischemia/infarction, and supraventricular arrhythmias after surgery. We reviewed the evidence regarding the effectiveness of perioperative ß-blockers for improving patient outcomes after cardiac and noncardiac surgery.

METHODS: Eleven large databases were searched from the time of their inception until October 2005. Various online-resources were consulted for the identification of unpublished trials and conference abstracts. We included randomized, controlled trials comparing perioperative ß-blockers with either placebo or the standard-of-care. Of the 3680 retrieved titles, 69 met inclusion criteria for analysis. Odds ratios (OR) assuming random effects were computed in the absence of significant clinical heterogeneity.

RESULTS: ß-Blockers reduced the frequency of ventricular tachyarrhythmias [OR (cardiac surgery): 0.28, 95% CI 0.13–0.57; OR (noncardiac surgery): 0.56, 95% CI 0.21–1.45], atrial fibrillation/flutter [OR (cardiac surgery): 0.37, 95% CI 0.28–0.48], other supraventricular arrhythmias [OR (cardiac surgery): 0.25, 95% CI 0.18–0.35; OR (noncardiac surgery): 0.43, 95% CI 0.14–1.37], and myocardial ischemia [OR (cardiac surgery): 0.49, 95% CI 0.17–1.4; OR (noncardiac surgery): 0.38, 95% CI 0.21–0.69]. Length of hospitalization was not reduced [weighted mean difference (cardiac surgery): –0.35 days, 95% CI –0.77–0.07; weighted mean difference (noncardiac surgery): –5.59 days, 95% CI –12.22–1.04] and, in contrast to previous reports, ß-blockers did not reduce mortality [OR (cardiac surgery): 0.55, 95% CI 0.17–1.83; OR (noncardiac surgery): 0.78, 95% CI 0.33–1.87], and they had no influence on the occurrence of perioperative myocardial infarction [OR (cardiac surgery): 0.89, 95% CI 0.53–1.5; OR (noncardiac surgery): 0.59; 0.25–1.39].

CONCLUSIONS: ß-Blockers reduced perioperative arrhythmias and myocardial ischemia, but they had no effect on myocardial infarction, mortality, or length of hospitalization.


   Introduction
Top
 Abstract
 Introduction
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Cardiovascular morbidity and mortality are common and costly complications for patients undergoing cardiac and noncardiac operations (1). Surgery for acquired cardiac disease is associated with mortality rates of up to 3%, and perioperative myocardial infarction (MI) rates of up to 6% (1). Moreover, atrial fibrillation complicates the postoperative course of up to 40% of patients undergoing cardiac surgery (2). In noncardiac surgical patients, cardiac death and/or MI occurs perioperatively in about 4% of patients (3). It is widely believed that heightened sympathetic nervous system activity plays a fundamental role in the development of perioperative cardiac complications, and that pharmacologic attenuation of this response leads to improved patient outcomes (4). In patients undergoing cardiac surgery, for example, ß-blockers are suggested to reduce the frequency of perioperative atrial fibrillation and other supraventricular arrhythmias (5,6). Recently, the American College of Chest Physicians issued recommendations to prescribe ß-blockers for the prevention of atrial fibrillation after cardiac surgery (7). It is, however, unknown whether perioperative ß-blockers can affect the major sequelae of atrial fibrillation, such as stroke or prolonged length of hospitalization (8).

ß-Blockers have also been recommended for patients undergoing noncardiac surgery as a means for reducing perioperative complications. A joint American College of Cardiology/American Heart Association task force, in fact, recommended ß-blocker treatment for high-risk individuals undergoing vascular surgery (9). Furthermore, Auerbach and Goldman (10) recommended expanding the indications for perioperative ß-blockers to high- and intermediate-risk patients undergoing any noncardiac operation. These recommendations were mainly based on two randomized trials, which found that ß-blockers reduced mortality and MI after noncardiac surgery (11,12). Other evidence regarding the effectiveness of ß-blockade on perioperative outcomes after noncardiac surgery are derived from small trials with conflicting results, or meta-analyses that have used mostly restrictive search techniques (13–15).

Thus, the aim of this study was to conduct a comprehensive meta-analysis to assess the effectiveness of ß-blockers for reducing perioperative cardiac morbidity and mortality for patients undergoing cardiac and noncardiac surgery. We further sought to assess the effects of perioperative ß-blocker treatment on length of hospitalization, cost of care, quality of life, and the frequency of adverse events related to their use.


   METHODS
Top
 Abstract
 Introduction
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
The search methods, as well as the approach to article review and inclusion, have been described previously (16). We included reports of randomized trials that compared ß-adrenoceptor-blockers with control (placebo or standard-care) in cardiac and noncardiac surgery. Articles were included if they studied the effect of ß-blockers on humans aged 18 yr or older. ß-Blockers had to be given preoperatively, intraoperatively, or up to 1 day after surgery. The duration of ß-blocker administration could be variable. In the case of multiple publication of a given cohort of patients, the first published article was included in our analysis. However, if a more recent publication corroborated the results of a larger cohort, longer follow-up, or both, we included this more recent publication.

We searched the following databases from their inception until October 2005 (dates of inception or publication are given in parentheses): Medline (1958), Embase (1974), Cochrane Central Register of Controlled Trials (CENTRAL)—Cochrane Anesthesia Group Specialized Register (2003, Issue 2), Biosis Previews (1970), CAB Abstracts (1972), Cumulative Index to Nursing and Allied Health Literature (CINAHL, 1982), Derwent Drug File (1964), Science Citation Index/Current Contents (1974), International Pharmaceutical Abstracts (1970), Pascal Biomed (1977) by computer enhanced search strategies (17,18), and we surveyed the reference lists of relevant articles. No language restrictions were applied. For the identification of trial results that were published in abstract form exclusively, we surveyed databases that include conference proceedings such as British Library Inside Conferences (1993), System for Information on Gray Literature in Europe (SIGLE, 1976), Conference Papers Index (CONFSCI, 1973), Index to Scientific and Technical Proceedings and Books (ISTBP, 1978), Index to Scientific and Technical Proceedings/Index to Social Sciences and Humanities Proceedings (ISTP/ISSHP, 1978), Biosis Previews (1970), and CAB Abstracts (1972). Furthermore, to identify studies that were not published because of negative results or other reasons, we referred to trial registers that are available online (16). Two reviewers independently evaluated whether articles met the inclusion criteria. A third reviewer was consulted in case of disagreement.

The following outcomes occurring until 30 days postoperatively or before discharge from hospital were considered as study end points: all-cause-mortality, MI (defined as an increase in myocardial isoenzymes or ST-elevation), myocardial ischemia (defined as significant ST segment depression), atrial fibrillation, other supraventricular arrhythmias, ventricular arrhythmias, cerebrovascular complications (verified by computed tomography scan or magnetic resonance imaging), congestive heart failure, bradycardia, and hypotension. Long-term all-cause-mortality was defined as deaths occurring after the 30th postoperative day or after discharge from hospital. Length of hospitalization was measured in days.

The following characteristics of study quality were assessed for their influence on the overall point estimates using meta-regression techniques: type of control group (placebo versus standard-care), method, and adequacy of randomization (true randomization versus quasirandomization). We assessed allocation concealment, blinding of the study, and description of withdrawals. Quality characteristics that influenced the effect size of ß-blockers in the meta-regression analysis ({alpha}-level of 0.05) are presented in a stratified analysis.

A statistical summary of treatment effects was presented in the absence of significant clinical heterogeneity. We used the "test of heterogeneity" at a significance level of P < 0.1, and the I2-statistic, which describes the proportion of variability due to heterogeneity between trials (19); an I2-statistic of 25% was chosen as a threshold between low and moderate heterogeneity (20). We considered two sources of heterogeneity between trials: a fluctuation of trial results around the true effect due to chance (statistical heterogeneity), and a difference in trial results due to variations inpatient or trial characteristics (clinical heterogeneity). Clinical heterogeneity was assessed by subgroup analysis using meta-regression for the following variables: age, gender, prevalence of coronary heart disease, previous MI, prevalence of hypertension, ejection fraction, prevalence of preoperative ß-blocker usage, and use of invasive hemodynamic monitoring. This analysis was done for all outcomes and is presented if one of these factors significantly influenced the effect of ß-blockers ({alpha}-level of 0.05). Odds ratios were calculated for dichotomous outcomes. A weighted mean difference (WMD) was calculated for length of hospitalization. All estimates were calculated using a random effects model (21). Publication bias was assessed using funnel plots, the Egger’s regression test (22), as well as the rank correlation test (23). When publication bias was judged to be present, we used the trim and fill method to assess the impact of publication bias on the overall effect estimate (24,25). Robustness of the model can be assessed when comparing the new estimate with the unadjusted estimate as a kind of sensitivity analysis. We used RevMan (version 4.2.7) and STATA (version 7) for data analysis.


   RESULTS
Top
 Abstract
 Introduction
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Description of studies
Our search retrieved 3680 titles, of which 3509 were judged to be irrelevant for our review. We obtained and reviewed the full-text versions of the remaining 171 studies. Of these, 70 trials were found to meet the preset inclusion criteria. One study was excluded during the review process because of multiple publication (Fig. 1) (26). Further specification of trial characteristics is given in Table 1.


Figure 18
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  		Figure 1. Flow chart of included and excluded studies.

 

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  		Table 1. Study Characteristics

 


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  		Table 1. Continued

 


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  		Table 1. Continued

 
All-Cause Mortality
Twenty-one trials studied all-cause mortality in 4404 participants (8,11,12,27–44). The average age of patients in these trials was 59 yr. Most trials evaluated 30-day mortality, except for Juul et al. (36) who had a median follow-up time of 18 mo. Our analysis found no effect of ß-blockers on mortality after cardiac and noncardiac surgery (cardiac surgery: OR 0.55, 95% CI 0.17–1.83; noncardiac surgery: OR 0.78, 95% CI 0.33–1.87) (Fig. 2).


Figure 28
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  		Figure 2. Effect of ß-blockers on perioperative all-cause mortality. Trials with no events specifically mentioned that they evaluated all-cause mortality. The central line displays an odds ratio of one (the value of no effect). Displayed are trial- and overall odds ratios with 95% confidence intervals. Effects are statistically significant if confidence intervals do not cross the central line.

 

Acute MI
Twenty-five trials studied the effect of ß-blockers on perioperative MI (before discharge from hospital) in 2723 participants (12,27,30,31,37,39,40,43–60). Mean age of these patients was 68 yr. The incidence of perioperative MI was unaffected by ß-blockers in cardiac and noncardiac surgery (cardiac surgery: OR 0.89, 95% CI 0.53–1.5; noncardiac surgery: OR 0.59, 95% CI 0.25–1.39) (Fig. 3). We found that the funnel plots depicting effect size versus trial precision were asymmetric, suggesting relevant publication bias, which was further substantiated by the rank correlation test (P = 0.037). By using the trim and fill method to adjust for potentially unpublished trials, we further attenuated the adjusted OR for the effect of ß-blockers on perioperative MI to 0.91 (95% CI 0.62–1.34), which indicates no significant beneficial effect of ß-blockers on MI (24,25).


Figure 38
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  		Figure 3. The effect of ß-blockers on the development of perioperative myocardial infarction. Trials with no events specifically mentioned that they evaluated myocardial infarction. The central line displays an odds ratio of one (the value of no effect). Displayed are trial- and overall odds ratios with 95% confidence intervals. Effects are statistically significant if confidence intervals do not cross the central line.

 

Myocardial Ischemia
Sixteen trials evaluated whether ß-blocker treatment attenuated intra- and postoperative myocardial ischemia in 2582 participants with a mean age of 60 yr (8,12,29,31,43,44,56–58,61–67). ß-Blockers reduced myocardial ischemia in patients undergoing noncardiac surgery (OR 0.38, 95% CI 0.21–0.69), whereas in cardiac surgery the effect was not statistically significant (OR 0.49, 95% CI 0.17–1.4) (Fig. 4). Meta-regression analysis showed that trials using standard care groups instead of placebo groups for comparison tended to report larger effects than placebo-controlled trials (Table 2).


Figure 48
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  		Figure 4. The effect of ß-blockers on the development of perioperative myocardial ischemia. Trials with no events specifically mentioned that they evaluated myocardial ischemia. The central line displays an odds ratio of one (the value of no effect). Displayed are trial- and overall odds ratios with 95% confidence intervals. Effects are statistically significant if confidence intervals do not cross the central line.

 

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  		Table 2. Trials Assessing Atrial Fibrillation and Myocardial Ischemia

 

Ventricular Arrhythmias
The effect of ß-blockers on the frequency of ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) was examined in 16 trials (8,27,29,31,34,41,47,48,50,58,63,68–72), which included 2571 participants with a mean age of 59 yr. The observational period usually started at inception of anesthesia and ended at discharge from hospital. Most investigators used a combined end point of ventricular tachycardia and ventricular fibrillation. Only four studies presented the individual rates for both types of ventricular arrhythmias (8,29,47,50). ß-Blockers significantly reduced the occurrence of ventricular arrhythmias for patients undergoing cardiac surgery (OR 0.28, 95% CI 0.13–0.57) (Fig. 5), whereas they did not significantly affect the occurrence of ventricular arrhythmias in noncardiac surgery (OR 0.56, 95% CI 0.21–1.45). Rates of ventricular fibrillation alone were not affected by ß-blockers in cardiac surgery (OR 0.29, 95% CI 0.07–1.25) (8,29,47,50). None of the noncardiac surgical trials reported on ventricular fibrillation. However, given the small sample size of only four trials, the analysis might have been under-powered to detect a change in ventricular fibrillation. Furthermore, ß-blockers significantly reduced the occurrence of ventricular premature beats in noncardiac surgery (OR 0.18, 95% CI 0.22–0.52); in cardiac surgery, this effect reached borderline significance (OR 0.59, 95% CI 0.35–1) (27,30,32,39,47,50,56,61,65,73–78).


Figure 58
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  		Figure 5. The effect of ß-blockers on the of the frequency of perioperative ventricular fibrillation and ventricular tachycardia. Trials with no events specifically mentioned that they evaluated these ventricular arrhythmias. The central line displays an odds ratio of one (the value of no effect). Displayed are trial- and overall odds ratios with 95% confidence intervals. Effects are statistically significant if confidence intervals do not cross the central line.

 

Atrial Fibrillation/Flutter, Supraventricular Arrhythmias
Twenty-six trials evaluated the effect of ß-blocker treatment on the frequency of postoperative atrial fibrillation or flutter in 4058 study participants with a mean age of 58 yr (8,27–29,37,38,41,43,46,50,55,69,72,75,76,79–89). Only the study by Bayliff et al. (29) was performed in a noncardiac surgical setting. The observational period usually started at induction of anesthesia and ended at the time of discharge from hospital. ß-Blockers reduced the odds of developing atrial fibrillation by 63% in cardiac surgery (OR 0.37, 95% CI 0.28–0.48) (Fig. 6). Meta-regression showed that trials using standard-care groups for comparison reported larger effects than that of placebo-controlled trials (Table 2). Most of the between-trial heterogeneity (I2 = 48.8%) observed in the data was due to this phenomenon. In the trial of patients undergoing noncardiac surgery, ß-blockers had no effect on the frequency of postoperative atrial fibrillation (OR of 0.59, 95% CI 0.13–2.6) (29). The effect of ß-blocker treatment on the frequency of supraventricular arrhythmias other than atrial fibrillation was studied in 3000 participants (27,29,30,32,35,42,45,47–53,59,68,69,71,75,78,81,84,88–91). These results showed that ß-blockers reduced the frequency of the arrhythmias after cardiac surgery (OR 0.25, 95% CI 0.2–0.39), but not after noncardiac operations (OR 0.43, 95% CI 0.14–1.37).


Figure 68
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  		Figure 6. The effect of ß-blockers on the frequency of perioperative atrial fibrillation/flutter in cardiac surgery. The central line delineates an odds ratio of one (the value of no effect). Displayed are trial- and overall odds ratios with 95% confidence intervals. Effects are statistically significant if confidence intervals do not cross the central line.

 

Length of Hospitalization
Eleven trials reported on length of hospitalization in 2330 participants with a mean age of 63 yr (8,30,31,33,38,58,59,69,81,82,90). ß-Blockers had no effect on length of hospitalization in either cardiac or noncardiac surgical trials. The WMD for cardiac surgery was –0.35 days (95% CI –0.77–0.07) (Fig. 7). Two trials reported on length of hospitalization after noncardiac surgery (31,58). Similarly to cardiac surgery, ß-blockers had no effect on length of hospitalization after noncardiac surgery (WMD –5.6 days, 95% CI –12.2–1.04).


Figure 78
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  		Figure 7. Effect of ß-blockers on length of hospital stay in cardiac surgery. The drugs did not significantly reduce length of stay in the evaluated trials. The central line delineates a mean difference of zero (the value of no effect). Displayed are trial- and overall differences in length of stay in days with 95% confidence intervals. Effects are statistically significant if confidence intervals do not cross the central line.

 

Other Adverse Events, Quality of Life, Cost of Care
The effects of ß-blockers on other adverse outcomes are summarized in Table 3. ß-Blockers significantly increased the risk of perioperative bradycardia and hypotension. Our search failed to find any trial that reported on quality of life. Only two trials reported hospital costs (8,33). The results of these trials were too heterogeneous to allow meaningful summary statistics.


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  		Table 3. The Effect of ß-blockers (as judged by the investigators) on Hemodynamically Significant Bradycardia and Hypotension (11,29,34,39,44,45,48,49,51,56,62,68,69,88,100,101), Radiologically Verified Cerebrovascular Events (8,31,34,51,58), and Clinically Verified Congestive Heart Failure (11,44,65,69)

 


   DISCUSSION
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
We performed a systematic review of the effectiveness of perioperative ß-blockers for the prevention of critical cardiovascular outcomes after cardiac and noncardiac surgery. Previous meta-analyses have evaluated the topic, but have used more restrictive search techniques. An overview of the characteristics of these studies and the current review are listed in Tables 4 and 5. In our review, we found that ß-blockers were effective for the prevention of arrhythmias and myocardial ischemia, but had no effect on the frequency of hard end-points like perioperative myocardial infarction, operative mortality, or length of hospitalization. There were insufficient data to evaluate whether ß-blockers influence quality of life or costs.


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  		Table 4. The Most Recent Previous Reviews on Noncardiac Surgery Compared to the Noncardiac Surgery Part of this Analysis

 


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  		Table 5. The Most Recent Previous Review on Cardiac Surgery Trials Compared to the Cardiac Surgery Part of this Analysis

 
Ventricular and Atrial Arrhythmias
The greatest beneficial effect of ß-blockers on perioperative outcomes observed were in the reduction of arrhythmias. We observed that ß-blockers reduced the frequency of life-threatening perioperative ventricular arrhythmias in patients undergoing cardiac surgery. Most authors did not specify the type of ventricular arrhythmia in their presentation, but it is reasonable to assume that these events mainly represented ventricular tachycardias, the more common arrhythmia. Hence, whether ß-blockers can also reduce the frequency of ventricular fibrillation is unknown.

There seemed to be no benefit on ventricular arrhythmias for patients undergoing noncardiac surgery. The causes for this differential effect in cardiac and noncardiac surgery are not entirely clear. Ventricular arrhythmias seem to be equally common in both surgical settings, with incidence rates up to 36%, depending on the stringency of the definitions (92,93). The subgroup of noncardiac surgical trials included only 512 patients, whereas the studies on cardiac surgery comprised 2059 patients. Our analysis of noncardiac surgical trials may thus have been under-powered to detect a significant antiarrhythmic effect of ß-blockers.

ß-Blockers were further found to reduce the incidence of atrial fibrillation after cardiac surgery. This finding is in agreement with a meta-analysis and the latest recommendations of the American College of Chest Physicians (6,7). Nevertheless, we found that much of the heterogeneity in the data could be attributed to whether the control group included patients receiving blinded placebo versus institutional standard-care. Standard-care trials tended to over-estimate the protective effect of ß-blockers. Reasons for a larger effect in standard-care trials are a lack of blinding of patients and doctors and a subsequent detection bias. Therefore, the observed effect size obtained from placebo-controlled trials (OR 0.62, 95% CI 0.51–0.76) should be regarded as a more valid estimate of the true effect. ß-Blocker withdrawal has been found to increase the frequency of postoperative atrial fibrillation (28). Seventy percent of control-patients in the trials included in our analysis were receiving ß-blockers preoperatively, and whether the ß blockers were continued after surgery or withdrawn for the purpose of the study is not always clearly stated (8,27–29,37,38,41,43,46,50,55,69,72,75,76,79–89). Thus, it is possible that ß-blocker withdrawal in the control groups might have led to higher rates of atrial fibrillation than in the ß-blocker groups.

MI and Ischemia
Two trials reported a reduction of MI by ß-blockers (12,14). In contrast to these reports, we found that ß-blockers had no beneficial effect in reducing the frequency of perioperative MI after both cardiac- and noncardiac surgery. In the vascular surgical trial by Poldermans et al. (12), 9 of 53 patients in the standard care group experienced nonfatal MIs, whereas none of 59 ß-blocker-treated patients had a MI. This high event rate in control patients might have inflated the effect of ß-blockers on MI observed in this trial. In a meta-analysis of eight noncardiac surgery trials that included 673 participants, Stevens et al. (14) reported that the odds of developing nonfatal perioperative MI could be reduced up to 81% by ß-blockers (14). However, we found evidence that these data are distorted by publication bias, which was not acknowledged by Stevens et al.

Furthermore, we found that ß-blockers reduce the risk for perioperative myocardial ischemia, which is in contrast to previous analysis (94). One explanation for this finding is that though ß-blockers reduce sympathetic nervous activation, and thereby reduce myocardial ischemia via their antiischemic properties, they have no clinically relevant antithrombotic potential, and thus may not prevent thrombotic events such as MI (95).

Mortality
We found no protective effect of ß-blockers against mortality for patients undergoing cardiac surgery. This might be due, in part, to low reported mortality rates in the identified cardiac surgery trials (only 10 deaths occurred in more than 2300 patients). In light of this low frequency of end points, and because these mortality rates may not reflect those from a real-life setting (96,97), no valid inferences can be drawn from the current literature on mortality in cardiac surgery. In noncardiac surgery, ß-blockers also had no protective effect against perioperative mortality. These findings contrast with the results of three landmark trials that showed that ß-blockers reduce mortality in noncardiac surgery (11–13). Poldermans et al. (12), for example, studied the effect of bisoprolol on mortality in 112 individuals at high cardiovascular risk undergoing vascular surgery. This unblinded trial was stopped early before the calculated sample size of 266 patients was reached because of a significant difference in this end point between groups at interim analysis. Again, the control group of this trial experienced unusually high event rates, which might have contributed to the remarkable risk reduction of 91% reported by the authors. Mangano et al. (11) studied the effect of atenolol on long-term mortality in 200 patients undergoing various noncardiac operations. The trial was criticized for including only end points occurring after ß-blocker therapy had already been stopped. A true intention-to-treat analysis should have also included the six early postoperative deaths during administration of the study medication. The recently published observational trial by Lindenauer et al. (13) found that ß-blockers improved survival in noncardiac surgical patients at high perioperative risk, whereas in patients at low risk, a harmful effect was observed. In contrast to these latter findings, we did not observe an influence of preoperative rates of previous MI, coronary heart disease, hypertension, and ejection fraction on the effect of ß-blockers.

Our findings of no beneficial effect of ß-blockers thus has particular clinical relevance, because these three aforementioned trials have provided a strong rationale for advocates of the use of ß-blockers in noncardiac surgery. Of relevance is the finding that other randomized trials that tried to reproduce the findings of Poldermans et al. (98), Managano et al. (11), and Lindenauer et al. (13) have failed to confirm the cardioprotective effects of perioperative ß-blockers. Current studies, such as the Perioperative Ischemic Evaluation (POISE) trial of perioperative cardiovascular mortality involving 10,000 participants, hopefully will elucidate the role of ß-blockers in noncardiac surgery (99).

Limitations
Most of the limitations of our study relate to the definition and assessment of outcomes. Arrhythmias were not assessed consistently in all trials. Some authors used Holter monitoring, whereas others only used scheduled electrocardiogram recordings. Therefore, some arrhythmias might have gone undetected in some trials. Furthermore, length of hospitalization is influenced by factors other than perioperative complications, is often controlled by practices of local health systems, and is affected by temporal changes and economic resources. Consequently, there is a wide range in average length of hospitalization among the different trials.


   CONCLUSIONS
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Current evidence suggests that perioperative ß-blockers reduce ventricular and supraventricular arrhythmias after cardiac surgery, and myocardial ischemia after noncardiac surgery. In contrast, the literature does not support a protective effect of perioperative ß-blockers against MI, overall mortality or length of stay. Moreover, these drugs increase the rates of perioperative hypotension and bradycardia. We have found no trial reporting on quality of life.


   ACKNOWLEDGMENT
 
We would like to thank Dr. Padma Shetty for her insightful comments on our manuscript.


   Footnotes
 
Accepted for publication September 15, 2006.


   REFERENCES
Top
 Abstract
 Introduction
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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