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From the Departments of *Anesthesia, and Health Policy Management, and Evaluation/Clinical Epidemiology, Toronto General Hospital and University of Toronto, Toronto, Ontario.
Address correspondence and reprint requests to W. Scott Beattie, MD, PhD, FRCPC, Department of Anesthesia, Toronto General Hospital and University of Toronto, EN 3-450 200 Elizabeth St., Toronto, Ontario M5G 2C4, Canada. Address e-mail to scott.beattie{at}uhn.on.ca.
Abstract
BACKGROUND: Recent meta-analyses assessing the efficacy of perioperative β-blockade trials have failed to show a reduction in postoperative morbidity and mortality. Tight control of heart rate (HR) has been suggested to improve these outcomes. Meta-analyses have not considered the influence of tight HR control on the efficacy of perioperative β-blockade.
METHODS: Using previously published search strategies, we identified all randomized trials evaluating perioperative β-blockers after noncardiac surgery. This search yielded 10 trials with 2176 patients. We used the data from these studies to correlate measures of HR control with major postoperative outcomes, primarily in-hospital myocardial infarction (MI). Odds ratio (OR) and 95% confidence intervals (CI) were calculated, and metaregression was performed correlating measures of HR control with MI.
RESULTS: The combined results of all studies did not show a significant cardioprotective effect of β-blockers, with considerable heterogeneity among the studies (OR = 0.76; 95% CI = 0.4–1.4; P = 0.38 heterogeneity: I2 = 34%). However, grouping the trials on the basis of maximal HR showed that trials where the estimated maximal HR was <100 bpm were associated with cardioprotection (OR = 0.23; 95% CI = 0.08–0.65; P = 0.005) whereas trials where the estimated maximal HR was >100 bpm did not demonstrate cardioprotection (OR = 1.17; 95% CI = 0.79–1.80; P = 0.43) with no heterogeneity. Moreover, metaregression of the HR response to β-blockade against the log OR of postoperative MI demonstrated a linear association between the effect of β-blockade on the mean, maximal, and variation in HR and the OR of an MI (r2 = 0.63; P < 0.001) where a larger effect of β-blockers on HR was associated with a decreased incidence of postoperative MI. Across all studies, β-blockade resulted in a reduction in postoperative HR (weighted mean difference: 8.6 bpm; 95% CI = –9.6 to –7.6; I2 = 85.3%) with considerable heterogeneity. This large heterogeneity in HR response to β-blockade was found to be related, in part, to the type of β-blocker, specifically, metoprolol, and the concomitant use of calcium channel blockers. Calcium channel blocker use and β-blockers other than metoprolol resulted in more effective control of HR. There was wide variability in the HR response to β-blockade. Twenty-five percent of patients receiving β-blockers had episodes when the HRs were more than 100 bpm, although 15% of placebo patients also had bradycardia, which would have required a dose reduction had they been administered β-blockers. Finally, this analysis found that perioperative β-blockade was associated with an increased incidence of bradycardia (OR = 3.49; 95% CI = 2.4–5.9) and congestive heart failure (OR = 1.68; 95% CI = 1.00–2.8).
CONCLUSIONS: The trials that achieve the most effective control of HR are associated with a reduced incidence of postoperative MI, suggesting that effective control of HR is important for achieving cardioprotection. Second, this analysis demonstrates that administration of β-blockers does not reliably decrease HRs in all patients, and may be associated with increased side effects. Judicious use of combination therapy with other drugs may be necessary to achieve effective postoperative control of HR.
This article has been cited by other articles:
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  J. W. Sear, J. W. Giles, G. Howard-Alpe, and P. Foex Perioperative beta-blockade, 2008: What does POISE tell us, and was our earlier caution justified? Br. J. Anaesth., August 1, 2008; 101(2): 135 - 138. [Full Text] [PDF]
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 M. J. London Quo Vadis, Perioperative Beta Blockade? Are You "POISE'd" on the Brink? Anesth. Analg., April 1, 2008; 106(4): 1025 - 1030. [Full Text] [PDF]
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