Variations in pharmacology of β-blockers may contribute to heterogeneous results in trials of perioperative β-blockade

Abstract

Background: Randomized controlled trials and meta-analyses provide conflicting guidance on the role of β-adrenergic receptor blockers (β-blockers) in reducing perioperative complications. We hypothesize that variability in trial results may be due in part to heterogeneous properties ofβ-blockers. First, we propose that the extent of β-blocker metabolism by cytochrome P-450 and the time available to titrate the dosage before surgery (titration time) may interact; dependence on P-450 may be most harmful when titration time is short. Second, β-blockers vary in their selectivity for the β-1 receptor and reduced selectivity may contribute to cerebral ischemia. Methods: We used meta-analysis and meta-regression of existing trials to explore the role of these pharmacological properties. Results: We found that both of these pharmacological factors are significantly associated with reduced efficacy of β-blockers. Conclusions: Pharmacological properties of β-blockers may contribute to heterogeneous trial results. Many trials have used metoprolol, which is extensively metabolized by cytochrome P450 and is less selective for the β-1 receptor. For these two reasons, the efficacy of metoprolol to prevent perioperative cardiac complications should be compared with the efficacy of other β-blockers. Copyright © 2010, the American Society of Anesthesiologists, Inc.