title: Variations in pharmacology of beta-blockers may contribute to heterogeneous results in trials of perioperative beta-blockade.
abstract: BACKGROUND
  Randomized controlled trials and meta-analyses provide conflicting guidance on the role of beta-adrenergic receptor blockers (beta-blockers) in reducing perioperative complications. We hypothesize that variability in trial results may be due in part to heterogeneous properties of beta-blockers. First, we propose that the extent of beta-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, beta-blockers vary in their selectivity for the beta-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 beta-blockers.
  
  
  CONCLUSIONS
  Pharmacological properties of beta-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 beta-1 receptor. For these two reasons, the efficacy of metoprolol to prevent perioperative cardiac complications should be compared with the efficacy of other beta-blockers.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio, and Audie L. Murphy Memorial Veterans Affairs Hospital, San Antonio, Texas, USA. rbadgett@kumc.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Badgett
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Lawrence
authors.forename: Steven L
authors.initials: SL
authors.lastname: Cohn
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D019990:Perioperative Care / Q000379:methods; D011110:Polymorphism, Genetic / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic / Q000379:methods
chemical_list: D000319:Adrenergic beta-Antagonists; D019389:Cytochrome P-450 CYP2D6